| 1. |
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| 2. |
- Grillner, Sten, et al.
(författare)
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Modeling a vertebrate motor system : pattern generation, steering and control of body orientation
- 2007
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Ingår i: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 165, s. 221-234
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Forskningsöversikt (refereegranskat)abstract
- The lamprey is one of the few vertebrates in which the neural control system for goal-directed locomotion including steering and control of body orientation is well described at a cellular level. In this report we review the modeling of the central pattern-generating network, which has been carried out based on detailed experimentation. In the same way the modeling of the control system for steering and control of body orientation is reviewed, including neuromechanical simulations and robotic devices.
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| 3. |
- Jankowska, Elzbieta
(författare)
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A neuronal system of movement control via muscle spindle secondaries
- 1989
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Ingår i: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 80, s. 299-303
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Forskningsöversikt (refereegranskat)abstract
- A recently discovered spinal interneuronal system of movement control is briefly described. It includes a population of midlumbar interneurones with a predominant monosynaptic input from secondary muscle spindle afferents but supplied with information via several other afferent and descending neuronal systems as well. The neurones are in direct contact with both motoneurones and other interneurones. The evidence in favour for their involvement in locomotion is briefly summarized. © 1989, Elsevier B.V.
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| 4. |
- Nyberg, Fred, et al.
(författare)
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Neuropeptides in hyperthermia
- 2007
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Ingår i: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 162, s. 277-293
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Forskningsöversikt (refereegranskat)abstract
- Brain damage as a result of hyperthermia or heat-stress has been the focus of attention in many areas of neuroscience in recent years. Heat-induced alterations in structural components of the central nervous system (CNS) will obviously also influence the relevant transmitter systems, which may be involved in a variety of different behaviors. Indeed, many studies have indicated that excitatory amino acids, and monoaminergic and peptidergic systems are affected during hyperthermia. This chapter will address past and current research on various neuropeptides that have been implicated in the consequences of hyperthermia and various other heat disorders. However, considering the large and even increasing number of identified neuroactive peptides, it is necessary to limit this chapter to a few peptides or peptide systems, which have received particular attention in relation to hyperthermia. Among these are the opioid peptides, the tachykinins, calcitonin gene-related peptide (CGRP), and peptides belonging to the angiotensin system. Most of these neuropeptides are not only affected by hyperthermia and abnormal alterations in the body temperature but also are involved in the endogenous mechanisms of regulating body temperature. This review does not endeavor to fully cover the field but it does aim to give the reader an idea of how various neuropeptides may be involved in the control of body heat and how peptidergic systems are affected during various thermal changes, including both immediate and long-term consequences.
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| 5. |
- Persson, Jonas, et al.
(författare)
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Altered brain activity in healthy seniors : what does it mean?
- 2006
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Ingår i: Progress in Brain Research. - Amsterdam : Elsevier. - 0079-6123 .- 1875-7855. ; 157, s. 45-56
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Age-related performance decreases are frequently observed on various memory tasks. Recent brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggest a link between altered patterns of brain activity in older adults and memory performance. Convergent neuroimaging evidence shows that older adults have decreased activity in multiple regions important for memory tasks. Such relative under-activation in older adults is likely related to age-related reductions in cognitive performance. Age-comparative neuroimaging studies have also provided convincing support for regional over-activation by older adults. Such findings indicate that the older brain can re-organize to better cope with cognitive and other challenges. Although over-activation may play a compensatory role when cognitive decline is limited, under-activation seems to be the typical pattern when cognitive impairment is in a more progressed state. This pattern of age-related changes suggests that compensation through over-activation is restricted to the early stages of cognitive impairment in aging.
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| 6. |
- Sharma, Hari Shanker, et al.
(författare)
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Blood-cerebrospinal fluid barrier in hyperthermia
- 2007
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Ingår i: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 162, s. 459-478
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Forskningsöversikt (refereegranskat)abstract
- The blood-CSF barrier (BCSFB) in choroid plexus works with the blood-brain barrier (BBB) in cerebral capillaries to stabilize the fluid environment of neurons. Dysfunction of either transport interface, i.e., BCSFB or BBB, causes augmented fluxes of ions, water and proteins into the CNS. These barrier disruptions lead to problems with edema and other compromised homeostatic mechanisms. Hyperthermic effects on BCSFB permeability and transport are not as well known as for BBB. However, it is becoming increasingly appreciated that elevated prostaglandin synthesis from fever/heat activation of cyclooxygenases (COXs) in the BCSFB promotes water and ion transfer from plasma to the ventricles; this harmful fluid movement into the CSF-brain interior can be attenuated by agents that inhibit the COXs. Moreover, new functional data from our laboratory animal model indicate that the BCSFB (choroidal epithelium) and the CSF-bordering ependymal cells are vulnerable to whole body hyperthermia (WBH). This is evidenced from the fact that rats subjected to 4h of heat stress (38 degrees C) showed a significant increase in the translocation of Evans blue and (131)Iodine from plasma to cisternal CSF, and manifested blue staining of the dorsal surface of the hippocampus and caudate nucleus. Degeneration of choroidal epithelial cells and underlying ependyma, a dilated ventricular space and damage to the underlying neuropil were frequent. A disrupted BCSFB is associated with a marked increase in edema formation in the hippocampus, caudate nucleus, thalamus and hypothalamus. Taken together, these findings suggest that the breaching of the BCSFB in hyperthermia significantly contributes to cell and tissue injuries in the CNS.
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| 7. |
- Sharma, Hari Shanker
(författare)
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Interaction between amino acid neuro transmitters and opioid receptors in hyperthermia-induced brain pathology
- 2007
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Ingår i: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 162, s. 295-317
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Forskningsöversikt (refereegranskat)abstract
- This review is focused on the possible interaction between amino acid neurotransmitters and opioid receptors in hyperthermia-induced brain dysfunction. A balance between excitatory and inhibitory amino acids appears to be necessary for normal brain function. Increased excitotoxicity and a decrease in inhibitory amino acid neurotrarismission in hyperthermia are associated with brain pathology and cognitive impairment. This is supported by recent data from our laboratory that show a marked increase in glutamate and aspartate and a decrease in GABA and glycine in several brain areas following heat stress at the time of brain pathology. Blockade of multiple opioid receptors with naloxone restored the heat stress-induced decline in GABA and glycine and thwarted the elevation of glutamate and aspartate in the CNS. In naloxone-treated stressed animals, cognitive dysfunction and brain pathology are largely absent. Taken together, these new findings suggest that an intricate balance between excitatory and inhibitory amino acids is important for brain function in heat stress. In addition, opioid receptors play neuromodulatory roles in amino acid neurotransmission in hyperthermia.
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| 8. |
- Sharma, Hari Shanker
(författare)
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Methods to produce hyperthermia-induced brain dysfunction
- 2007
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Ingår i: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 162, s. 173-199
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Forskningsöversikt (refereegranskat)abstract
- The recent increase in the frequency and intensity of killer heat waves across the globe has aroused worldwide medical attention to exploring therapeutic strategies to attenuate heat-related morbidity and/or mortality. Death due to heat-related illnesses often exceeds >50% of heat victims. Those who survive are crippled with lifetime disabilities and exhibit profound cognitive, sensory, and motor dysfunction akin to premature neurodegeneration. Although more than 50% of the world populations are exposed to summer heat waves; our understanding of detailed underlying mechanisms and the suitable therapeutic strategies have still not been worked out. One of the basic reasons behind this is the lack of a reliable experimental model to simulate clinical hyperthermia. This chapter describes a suitable animal model to induce hyperthermia in rats (or mice) comparable to the clinical situation. The model appears to be useful for studying the effects of heat-related illnesses on changes in various organs and systems, including the central nervous system (CNS). Since hyperthermia is often associated with profound brain dysfunction, additional methods to examine some crucial parameters of brain injury, e.g., blood-brain barrier (BBB) breakdown and brain edema formation, are also described.
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| 9. |
- Sharma, Hari Shanker, et al.
(författare)
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Nanoparticles aggravate heat stress induced cognitive deficits, blood-brain barrier disruption, edema formation and brain pathology
- 2007
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Ingår i: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 162, s. 245-273
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Forskningsöversikt (refereegranskat)abstract
- Our knowledge regarding the influence of nanoparticles on brain function in vivo during normal or hyperthermic conditions is still lacking. Few reports indicate that when nanoparticles enter into the central nervous system (CNS) they may induce neurotoxicity. On the other hand, nanoparticle-induced drug delivery to the brain enhances neurorepair processes. Thus, it is likely that the inclusion of nanoparticles in body fluid compartments alters the normal brain function and/or its response to additional stress, e.g., hyperthermia. New data from our laboratory show that nanoparticles derived from metals (e.g., Cu, Ag or Al, approximately 50-60nm) are capable of inducing brain dysfunction in normal animals and aggravating the brain pathology caused by whole-body hyperthermia (WBH). Thus, normal animals treated with nanoparticles (for 1 week) exhibited mild cognitive impairment and cellular alterations in the brain. Subjection of these nanoparticle-treated rats to WBH resulted in profound cognitive and motor deficits, exacerbation of blood-brain barrier (BBB) disruption, edema formation and brain pathology compared with naive animals. These novel observations suggest that nanoparticles enhance brain pathology and cognitive dysfunction in hyperthermia. The possible mechanisms of nanoparticle-induced exacerbation of brain damage in WBH and its functional significance in relation to our current knowledge are discussed in this review.
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| 10. |
- Sharma, Hari Shanker, et al.
(författare)
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Nanoparticles influence pathophysiology of spinal cord injury and repair
- 2009
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Ingår i: Progress in Brain Research. - Amsterdam : Elsevier. - 0079-6123 .- 1875-7855. - 9780444534316 ; 180, s. 155-180
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Forskningsöversikt (refereegranskat)abstract
- Spinal cord injury (SCI) is a serious clinical problem for which no suitable therapeutic strategies have been worked out so far. Recent studies suggest that the SCI and its pathophysiological responses could be altered by systemic exposure to nanoparticles. Thus, SCI when made in animals intoxicated with engineered nanoparticles from metals or silica dust worsened the outcome. On the other hand, drugs tagged with titanium (TiO2) nanoparticles or encapsulated in liposomes could enhance their neuroprotective efficacy following SCI. Thus, to expand our knowledge on nanoparticle-induced alterations in the spinal cord pathophysiology further research is needed. These investigations will help to develop new strategies to achieve neuroprotection in SCI, for example, using nanodrug delivery. New results from our laboratory showed that nanoparticle-induced exacerbation of cord pathology following trauma can be reduced when the suitable drugs tagged with TiO2 nanowires were administered into the spinal cord as compared to those drugs given alone. This indicates that nanoparticles depending on the exposure and its usage could induce both neurotoxicity and neuroprotection. This review discusses the potential adverse or therapeutic utilities of nanoparticles in SCI largely based on our own investigations. In addition, possible mechanisms of nanoparticle-induced exacerbation of cord pathology or enhanced neuroprotection following nanodrug delivery is described in light of recently available data in this rapidly emerging field of nanoneurosciences.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Kuter, Katarzyna Z., et al.
(författare)
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The role of glia in Parkinson's disease : Emerging concepts and therapeutic applications
- 2020
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Ingår i: Recent Advances in Parkinson's Disease. - : Elsevier. - 0079-6123 .- 1875-7855. - 9780444642608 ; 252, s. 131-168
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Bokkapitel (refereegranskat)abstract
- Originally believed to primarily affect neurons, Parkinson's disease (PD) has recently been recognized to also affect the functions and integrity of microglia and astroglia, two cell categories of fundamental importance to brain tissue homeostasis, defense, and repair. Both a loss of glial supportive-defensive functions and a toxic gain of glial functions are implicated in the neurodegenerative process. Moreover, the chronic treatment with L-DOPA may cause maladaptive glial plasticity favoring a development of therapy complications. This chapter focuses on the pathophysiology of PD from a glial point of view, presenting this rapidly growing field from the first discoveries made to the most recent developments. We report and compare histopathological and molecular findings from experimental models of PD and human studies. We moreover discuss the important role played by astrocytes in compensatory adaptations taking place during presymptomatic disease stages. We finally describe examples of potential therapeutic applications stemming from an increased understanding of the important roles of glia in PD.
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| 15. |
- Niu, Feng, et al.
(författare)
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Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury
- 2021
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Ingår i: Progress in Brain Research. - Amsterdam : Elsevier. - 0079-6123 .- 1875-7855. ; 265, s. 139-230, s. 139-230
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Tidskriftsartikel (refereegranskat)abstract
- Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims.Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury.In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.
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| 16. |
- Petersson, Per, et al.
(författare)
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Basal ganglia oscillations as biomarkers for targeting circuit dysfunction in Parkinson's disease
- 2020
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Ingår i: Recent advances in Parkinson's disease. - : Elsevier. - 1875-7855 .- 0079-6123. - 9780444642608 ; , s. 525-557
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Bokkapitel (refereegranskat)abstract
- Oscillations are a naturally occurring phenomenon in highly interconnected dynamical systems. However, it is thought that excessive synchronized oscillations in brain circuits can be detrimental for many brain functions by disrupting neuronal information processing. Because synchronized basal ganglia oscillations are a hallmark of Parkinson's disease (PD), it has been suggested that aberrant rhythmic activity associated with symptoms of the disease could be used as a physiological biomarker to guide pharmacological and electrical neuromodulatory interventions. We here briefly review the various manifestations of basal ganglia oscillations observed in human subjects and in animal models of PD. In this context, we also review the evidence supporting a pathophysiological role of different oscillations for the suppression of voluntary movements as well as for the induction of excessive motor activity. In light of these findings, it is discussed how oscillations could be used to guide a more precise targeting of dysfunctional circuits to obtain improved symptomatic treatment of PD.
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| 17. |
- Sahib, Seaab, et al.
(författare)
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Nanodelivery of traditional Chinese Gingko Biloba extract EGb-761 and bilobalide BN-52021 induces superior neuroprotective effects on pathophysiology of heat stroke
- 2021
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Ingår i: Progress in Brain Research. - : Elsevier. - 0079-6123 .- 1875-7855. ; 265, s. 249-315, s. 249-315
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Tidskriftsartikel (refereegranskat)abstract
- Military personnel often exposed to high summer heat are vulnerable to heat stroke (HS) resulting in abnormal brain function and mental anomalies. There are reasons to believe that leakage of the blood-brain barrier (BBB) due to hyperthermia and development of brain edema could result in brain pathology. Thus, exploration of suitable therapeutic strategies is needed to induce neuroprotection in HS. Extracts of Gingko Biloba (EGb-761) is traditionally used in a variety of mental disorders in Chinese traditional medicine since ages. In this chapter, effects of TiO2 nanowired EGb-761 and BN-52021 delivery to treat brain pathologies in HS is discussed based on our own investigations. We observed that TiO2 nanowired delivery of EGb-761 or TiO2 BN-52021 is able to attenuate more that 80% reduction in the brain pathology in HS as compared to conventional drug delivery. The functional outcome after HS is also significantly improved by nanowired delivery of EGb-761 and BN-52021. These observations are the first to suggest that nanowired delivery of EGb-761 and BN-52021 has superior therapeutic effects in HS not reported earlier. The clinical significance in relation to the military medicine is discussed.
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| 18. |
- Sharma, Aruna, et al.
(författare)
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Histamine H3 and H4 receptors modulate Parkinson's disease induced brain pathology : Neuroprotective effects of nanowired BF-2649 and clobenpropit with anti-histamine-antibody therapy
- 2021
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Ingår i: Brain protection strategies and nanomedicine. - : Elsevier BV. - 9780323989275 ; 266, s. 1-73
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Bokkapitel (refereegranskat)abstract
- Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibers in substantia nigra pars Compacta (SNpc), striatum (STr) and caudate putamen (CP) associated with upregulation of Histamine H3 receptors and downregulation of H4 receptors in human cases of PD is observed in postmortem cases. These findings indicate that modulation of histamine H3 and H4 receptors and/or histaminergic transmission may induce neuroprotection in PD induced brain pathology. In this review effects of a potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist, in association with monoclonal anti-histamine antibodies (AHmAb) in PD brain pathology is discussed based on our own observations. Our investigation shows that chronic administration of conventional or TiO2 nanowired BF 2649 (1 mg/kg, i.p.) or CLBPT (1 mg/kg, i.p.) once daily for 1 week together with nanowired delivery of HAmAb (25 mu L) significantly thwarted ASNC and p-tau levels in the SNpC and STr and reduced PD induced brain pathology. These observations are the first to show the involvement of histamine receptors in PD and opens new avenues for the development of novel drug strategies in clinical strategies for PD, not reported earlier.
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| 19. |
- Sharma, Aruna, et al.
(författare)
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Topical application of CNTF, GDNF and BDNF in combination attenuates blood-spinal cord barrier permeability, edema formation, hemeoxygenase-2 upregulation, and cord pathology
- 2021
-
Ingår i: Brain protection strategies and nanomedicine. - : Elsevier BV. - 9780323989275 ; 266, s. 357-376
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Bokkapitel (refereegranskat)abstract
- Spinal cord injury (SCI) is one of the leading causes of disability in Military personnel for which no suitable therapeutic strategies are available till today. Thus, exploration of novel therapeutic measures is highly needed to enhance the quality of life of SCI victims. Previously, topical application of BDNF and GDNF in combination over the injured spinal cord after 90min induced marked neuroprotection. In present investigation, we added CNTF in combination with BDNF and/or GDNF treatment to examine weather the triple combination applied over the traumatic cord after 90 or 120min could thwart cord pathology. Since neurotrophins attenuate nitric oxide (NO) production in SCI, the role of carbon monoxide (CO) production that is similar to NO in inducing cell injury was explored using immunohistochemistry of the constitutive isoform of enzyme hemeoxygenase-2 (HO-2). SCI inflicted over the right dorsal horn of the T10-11 segments by making an incision of 2mm deep and 5mm long upregulated the HO-2 immunostaining in the T9 and T12 segments after 5h injury. These perifocal segments are associated with breakdown of the blood-spinal cord barrier (BSCB), edema development and cell injuries. Topical application of CNTF with BDNF and GDNF in combination (10ng each) after 90 and 120min over the injured spinal cord significantly attenuated the BSCB breakdown, edema formation, cell injury and overexpression of HO-2. These observations are the first to show that CNTF with BDNF and GDNF induced superior neuroprotection in SCI probably by downregulation of CO production, not reported earlier.
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| 20. |
- Sharma, Hari Shanker, et al.
(författare)
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Alzheimer's disease neuropathology is exacerbated following traumatic brain injury. Neuroprotection by co-administration of nanowired mesenchymal stem cells and cerebrolysin with monoclonal antibodies to amyloid beta peptide
- 2021
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Ingår i: Progress in Brain Research. - : Elsevier. - 0079-6123 .- 1875-7855. ; 265, s. 1-97, s. 1-97
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Tidskriftsartikel (refereegranskat)abstract
- Military personnel are prone to traumatic brain injury (TBI) that is one of the risk factors in developing Alzheimer's disease (AD) at a later stage. TBI induces breakdown of the blood-brain barrier (BBB) to serum proteins into the brain and leads to extravasation of plasma amyloid beta peptide (ΑβP) into the brain fluid compartments causing AD brain pathology. Thus, there is a need to expand our knowledge on the role of TBI in AD. In addition, exploration of the novel roles of nanomedicine in AD and TBI for neuroprotection is the need of the hour. Since stem cells and neurotrophic factors play important roles in TBI and in AD, it is likely that nanodelivery of these agents exert superior neuroprotection in TBI induced exacerbation of AD brain pathology. In this review, these aspects are examined in details based on our own investigations in the light of current scientific literature in the field. Our observations show that TBI exacerbates AD brain pathology and TiO2 nanowired delivery of mesenchymal stem cells together with cerebrolysin—a balanced composition of several neurotrophic factors and active peptide fragments, and monoclonal antibodies to amyloid beta protein thwarted the development of neuropathology following TBI in AD, not reported earlier.
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| 21. |
- Sharma, Hari Shanker, et al.
(författare)
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Methamphetamine exacerbates pathophysiology of traumatic brain injury at high altitude. Neuroprotective effects of nanodelivery of a potent antioxidant compound H-290/51
- 2021
-
Ingår i: Brain protection strategies and nanomedicine. - : Elsevier BV. - 9780323989275 ; 266, s. 123-193
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Bokkapitel (refereegranskat)abstract
- Military personnel are often exposed to high altitude (HA, ca. 4500-5000 m) for combat operations associated with neurological dysfunctions. HA is a severe stressful situation and people frequently use methamphetamine (METH) or other psychostimulants to cope stress. Since military personnel are prone to different kinds of traumatic brain injury (TBI), in this review we discuss possible effects of METH on concussive head injury (CHI) at HA based on our own observations. METH exposure at HA exacerbates pathophysiology of CHI as compared to normobaric laboratory environment comparable to sea level. Increased blood-brain barrier (BBB) breakdown, edema formation and reductions in the cerebral blood flow (CBF) following CHI were exacerbated by METH intoxication at HA. Damage to cerebral microvasculature and expression of beta catenin was also exacerbated following CHI in METH treated group at HA. TiO2-nanowired delivery of H-290/51 (150 mg/kg, i.p.), a potent chain-breaking antioxidant significantly enhanced CBF and reduced BBB breakdown, edema formation, beta catenin expression and brain pathology in METH exposed rats after CHI at HA. These observations are the first to point out that METH exposure in CHI exacerbated brain pathology at HA and this appears to be related with greater production of oxidative stress induced brain pathology, not reported earlier.
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| 22. |
- Sharma, Hari Shanker, et al.
(författare)
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Neuroprotective effects of insulin like growth factor-1 on engineered metal nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, edema formation, oxidative stress, upregulation of neuronal nitric oxide synthase and brain pathology
- 2021
-
Ingår i: Progress in Brain Research. - : Elsevier. - 0079-6123 .- 1875-7855. ; 266, s. 97-121, s. 97-121
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Tidskriftsartikel (refereegranskat)abstract
- Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing oxidative stress and/or nitric oxide production. This hypothesis was examined in the rat intoxicated with Ag, Cu or Al (50–60 nm) nanoparticles (50 mg/kg, i.p. once daily) for 7 days. In these NPs treated rats the BBB permeability, brain edema, neuronal nitric oxide synthase (nNOS) immunoreactivity and brain oxidants levels, e.g., myeloperoxidase (MP), malondialdehyde (MD) and glutathione (GT) was examined on the 8th day. Cu and Ag but not Al nanoparticles increased the MP and MD levels by twofold in the brain although, GT showed 50% decline. At this time increase in brain water content and BBB breakdown to protein tracers were seen in areas exhibiting nNOS positive neurons and cell injuries. Pretreatment with insulin like growth factor-1 (IGF-1) in high doses (1 μg/kg, i.v. but not 0.5 μg/kg daily for 7 days) together with NPs significantly reduced the oxidative stress, nNOS upregulation, BBB breakdown, edema formation and cell injuries. These novel observations demonstrate that (i) NPs depending on their metal constituent (Cu, Ag but not Al) induce oxidative stress and nNOS expression leading to BBB disruption, brain edema and cell damage, and (ii) IGF-1 depending on doses exerts powerful neuroprotection against nanoneurotoxicity, not reported earlier.
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| 23. |
- Sharma, Hari Shanker, et al.
(författare)
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Superior antioxidant and anti-ischemic neuroprotective effects of cerebrolysin in heat stroke following intoxication of engineered metal Ag and Cu nanoparticles : A comparative biochemical and physiological study with other stroke therapies
- 2021
-
Ingår i: Progress in Brain Research. - : Elsevier. - 0079-6123 .- 1875-7855. ; 266, s. 301-348, s. 301-348
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Tidskriftsartikel (refereegranskat)abstract
- Military personnel are often exposed to high environmental heat associated with industrial or ambient abundance of nanoparticles (NPs) affecting brain function. We have shown that engineered metal NPs Ag and Cu exacerbate hyperthermia induced brain pathology. Thus, exploration of novel drug therapy is needed for effective neuroprotection in heat stroke intoxicated with NPs. In this investigation neuroprotective effects of cerebrolysin, a balanced composition of several neurotrophic factors and active peptides fragments exhibiting powerful antioxidant and anti-ischemic effects was examined in heat stroke after NPs intoxication. In addition, its efficacy is compared to currently used drugs in post-stroke therapies in clinics. Thus, levertiracetam, pregabalin, topiramat and valproate were compared in standard doses with cerebrolysin in heat stroke intoxicated with Cu or Ag NPs (50–60 nm, 50 mg/kg, i.p./day for 7 days). Rats were subjected to 4 h heat stress (HS) in a biological oxygen demand incubator at 38 °C (Relative Humidity 45–47%; Wind velocity 22.4–25.6 cm/s) that resulted in profound increase in oxidants Luminol, Lucigenin, Malondialdehyde and Myeloperoxidase, and a marked decrease in antioxidant Glutathione. At this time severe reductions in the cerebral blood flow (CBF) was seen together with increased blood-brain barrier (BBB) breakdown and brain edema formation. These pathophysiological responses were exacerbated in NPs treated heat-stressed animals. Pretreatment with cerebrolysin (2.5 mL/kg, i.v.) once daily for 3 days significantly attenuated the oxidative stress, BBB breakdown and brain edema and improved CBF in the heat stressed group. The other drugs were least effective on brain pathology following heat stroke. However, in NPs treated heat stressed animals 5 mL/kg conventional cerebrolysin and 2.5 mL/kg nanowired cerebrolysin is needed to attenuate oxidative stress, BBB breakdown, brain edema and to improve CBF. Interestingly, the other drugs even in higher doses used are unable to alter brain pathologies in NPs and heat stress. These observations are the first to demonstrate that cerebrolysin is the most superior antioxidant and anti-ischemic drug in NPs exposed heat stroke, not reported earlier.
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| 24. |
- Björklund, A, et al.
(författare)
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Reafferentation of the subcortically denervated hippocampus as a model for transplant-induced functional recovery in the CNS
- 1990
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Ingår i: Progress in Brain Research. - 0079-6123. ; 83, s. 411-426
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Forskningsöversikt (refereegranskat)abstract
- Subcortical deafferentation of the hippocampal formation is known to induce profound behavioural deficits. Transplants of fetal septal or brainstem tissue are capable of restoring some aspects of normal physiological and behavioural function in subcortically deafferented (i.e. fimbria-fornix or septal lesioned) rats. Such grafts have been shown to re-establish extensive new afferent inputs to the denervated hippocampal formation. As shown for grafted cholinergic and noradrenergic neurons, the ingrowing axons form laminar innervation patterns which closely mimic those of the normal cholinergic and noradrenergic innervations. The ingrowth appears to be very precisely regulated by the denervated target: each neuron type produces distinctly different innervation patterns; the growth is inhibited by the presence of an intact innervation of the same type; and it is stimulated by additional denervating lesions. Both ultrastructually and electrophysiologically the graft-derived fibres have been seen to form extensive functional synaptic contacts. Biochemically, cholinergic septal grafts and noradrenergic locus coeruleus grafts restore transmitter synthesis and turnover in the reinnervated hippocampus. Intracerebral microdialysis has revealed that acetylcholine and noradrenaline release is restored to normal or supranormal levels in the graft-reinnervated hippocampus, and that the grafted neurons can be activated in a normal way from the host through behavioural activation induced by sensory stimulation or electrical stimulation of the lateral habenula. These results indicate that the grafted monoaminergic neurons can restore tonic regulatory neurotransmission at previously denervated synaptic sites even when they are implanted into the ectopic brain sites. Such functional reafferentation may be sufficient for at least partial restoration of function in the subcortically deafferented hippocampus.
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| 25. |
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| 26. |
- Dunnett, S. B, et al.
(författare)
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Preface
- 2017
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Ingår i: Functional Neural Transplantation IV Translation to Clinical Application, Part B. - 0079-6123. - 9780128138793 ; 231
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 27. |
- Dunnett, S., et al.
(författare)
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Preface
- 2017
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Ingår i: Functional Neural Transplantation IV Translation to Clinical Application, Part A. - 0079-6123. ; 230
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Ekerot, Carl-Fredrik, et al.
(författare)
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Chapter 24 The control of forelimb movements by intermediate cerebellum
- 1997
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Ingår i: Progress in brain research. - 0079-6123. - 0444801049 ; 114, s. 423-429
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In a series of studies, the functional organization of cerebellar regions contributing to the control of forelimb movements via the rubro- and corticospinal tracts has been characterized in the cat. The system consists of the cerebellar cortical C1, C3 and Y zones and their efferent intracerebellar nucleus, the interpositus anterior. Based on analyses of cutaneous and muscle afferent climbing fibre input, of corticonuclear connections and of limb movements controlled, a modular organization of this cerebellar control system is proposed. Each module consists of a number of cortical microzones, defined by their homogeneous climbing fibre input, and a group of neurones in nucleus interpositus anterior on which these microzones converge. The input to climbing fibres is multi-modal and originates from cutaneous A beta (tactile), A delta and C (nociceptive) fibres and from muscle afferents. The cutaneous receptive fields have spatial characteristics suggestive of a relation to elemental movements. For most climbing fibres, the spatial relationship between cutaneous and muscle afferent input is such that the muscle afferent input originates from muscles that, if activated, would tend to move the cutaneous receptive field of the climbing fibre towards a stimulus applied to the skin. By contrast, the limb movement controlled by the module often has the opposite direction, and would thus tend to move the cutaneous receptive field away from a stimulus applied to the skin. Functional implications of this organization for the involvement of these regions in acute and adaptive motor control of limb movements are discussed.
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| 29. |
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| 31. |
- Wieloch, Tadeusz
(författare)
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Neurochemical Correlates to Selective Neuronal Vulnerability
- 1985. - C
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Ingår i: Molecular Mechanisms of Ischemic Brain Damage. - 0079-6123. - 0444806547 ; 63, s. 69-85
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Bokkapitel (refereegranskat)abstract
- This chapter describes some of the special neurochemical features of the areas of the brain selectively vulnerable to ischemic and hypoglycemic insults. The chapter focuses on the neuronal connections to the vulnerable brain areas, on the distribution of receptors and transmitter content in the vulnerable areas, and on some current hypothesis of neuronal damage. Emphasis will be placed on a possible imbalance between excitation and inhibition of neurons as a factor in the development of neuronal necrosis, in particular the importance of excitatory transmitters, suggested to mediate ischemic and hypoglycemic brain damage. The amino acids glutamate and aspartate are major excitatory transmitters in the central neurons system. When present in high concentration they are neurotoxic and can play a role in the pathogenesis of several neurological diseases, such as temporal lobe epilepsy, Huntington's disease, and olivopontocerebellar dystrophy.
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| 32. |
- Wieloch, Tadeusz, et al.
(författare)
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Protein phosphorylation and the regulation of mRNA translation following cerebral ischemia
- 1993. - C
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Ingår i: Neurobiology of Ischemic Brain Damage. - 0079-6123. - 9780444896032 ; 96, s. 179-191
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Bokkapitel (refereegranskat)abstract
- This chapter discusses the changes in protein phosphorylation following ischemia, with particular reference to the regulation of the initiation of protein synthesis. Transient cerebral ischemia seems to induce a post-ischemic imbalance between protein kinase and protein phosphatase activities, leading to a net dephosphorylation of proteins in the vulnerable neurons. This imbalance may lead to the persistent changes in processes crucial for neuronal survival such as post-ischemic protein synthesis. The depression of protein synthesis after an ischemic insult most probably is because of a decreased guanine nucleotide exchange factor (GEF) activity, leading to a limited availability of eukaryotic initiation factors (eIF-2) for initiation complex formation. The inhibition of GEF activity in the vulnerable regions could in turn be because of dephosphorylation of GEF, possibly because of tyrosine phosphatase activation and a decreased casein kinase II activity. Post-ischemic inhibition of protein kinase C and calcium calmodulin kinase II may in addition depress eIF-4 activity leading to a selective translation of mRNA such as heat shock mRNA.
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| 49. |
- Karlsson, Ann-Katrin, 1950
(författare)
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Autonomic dysfunction in spinal cord injury: clinical presentation of symptoms and signs
- 2006
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Ingår i: Progress in Brain Research. - 0079-6123. ; 152, s. 1-8
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Forskningsöversikt (refereegranskat)abstract
- Spinal cord injury and especially cervical spinal cord injury implies serious disturbances in autonomic nervous system function. The clinical effects of these disturbances are striking. In the acute phase, the autonomic imbalance and its effect on cardiovascular, respiratory system and temperature regulation may be life threatening. Serious complications such as over-hydration with the risk of pulmonary edema or hyponatremia are seen. The cord-injured person suffers from autonomic nervous system dysfunction also affecting bladder and bowel control, renal and sexual function. Paralytic ileus may cause vomiting and aspiration, which in turn interferes with respiratory function in those with cervical spinal cord injury. The cord-injured person is at risk to develop pressure sores from the moment of the accident. Two to three months post-injury the cord-injured person with a lesion level above the fifth thoracic segment may develop autonomic dysreflexia, characterised by sympathetically mediated vasoconstriction in muscular, skin, renal and presumably gastrointestinal vascular beds induced by an afferent peripheral stimulation below lesion level. The reaction might cause cerebrovascular complications and has effects on metabolism. Some of the autonomic disturbances are transient and a new balance is reached months post-injury, while others persist for life.
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