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| 2. |
- Andersson, Heléne, 1973, et al.
(författare)
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Trauma-induced reactive gliosis is reduced after treatment with octanol and carbenoxolone
- 2011
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Ingår i: Neurological research. - 0161-6412. ; 33:6, s. 614-624
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reactive gliosis and scar formation after brain injury can inhibit the recovery process. As many glial cells utilize gap junctions for intercellular signaling, this study investigated whether two commonly used gap junction blockers, octanol and carbenoxolone, could attenuate reactive gliosis following a minor traumatic brain injury. Methods: Octanol (710 mg/kg) or carbenoxolone (90 mg/kg) was administered 30 minutes before or after a needle track injury in adult male Sprague-Dawley rats. To mark dividing cells, animals were injected with bromodeoxyuridine (BrdU; 150 mg/kg) intraperitoneally two times per day, 8 hours apart and killed 2 days later. Immunohistochemistry for BrdU and markers for reactive glial cells [glial fibrillary acidic protein (GFAP), ED1, and NG2] were investigated using immunohistochemistry and western blot techniques. Results: Two days after injury, increased cellular proliferation, activated astrocytes and microglia, and upregulation of NG2 expression were observed surrounding the injury site. Octanol and carbenoxolone administrated prior to injury significantly decreased cell proliferation by 60 and 70% respectively. The distance of GFAP immunoreactive astrocytes from the wound margin was decreased by 32 and 18% when octanol was administrated prior to or post injury respectively. Treatment with octanol also decreased the number of reactive microglia by 55% and, when administrated prior to injury, octanol reduced the distance of NG2 expression from the wound by 48%. Conclusion: The present study demonstrates that two important components of reactive gliosis, cellular activation and proliferation, can be attenuated by octanol and carbenoxolone.
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| 3. |
- Deshpande, J. K., et al.
(författare)
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Amelioration of ischaemic brain damage by postischaemic treatment with flunarizine
- 1985
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Ingår i: Neurological Research. - : Informa UK Limited. - 0161-6412 .- 1743-1328. ; 7:1, s. 27-29
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Tidskriftsartikel (refereegranskat)abstract
- The effect of flunarizine, a calcium entry blocker, on ischaemic damage was investigated using a new model of forebrain ischaemia. Fasted rats were subjected to nine minutes ischaemia and one week recovery. One group served as control; a second was pretreated orally with flunarizine; a third group received postischaemic flunarizine treatment Focussing on the hippocampus, an area of high susceptibility to ischaemic damage, we report that flunarizine treatment significantly reduced neuronal necrosis. Importantly, the amelioration of necrosis was also observed when flunarizine was administered 5 min following resumption of cerebral perfusion.
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| 4. |
- El-Habta, Roine, et al.
(författare)
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N-acetylcysteine increases dopamine release and prevents the deleterious effects of 6-OHDA on the expression of VMAT2, α-synuclein, and tyrosine hydroxylase
- 2024
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Ingår i: Neurological Research. - : Taylor & Francis Group. - 0161-6412 .- 1743-1328. ; 46:5, s. 406-415
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Current treatments for Parkinson’s disease using pharmacological approaches alleviate motor symptoms but do not prevent neuronal loss or dysregulation of dopamine neurotransmission. In this article, we have explored the molecular mechanisms underlying the neuroprotective effect of the antioxidant N-acetylcysteine (NAC) on the damaged dopamine system.Methods: SH-SY5Y cells were differentiated towards a dopaminergic phenotype and exposed to 6-hydroxydopamine (6-OHDA) to establish an in vitro model of Parkinson’s disease. We examined the potential of NAC to restore the pathological effects of 6-OHDA on cell survival, dopamine synthesis as well as on key proteins regulating dopamine metabolism. Specifically, we evaluated gene- and protein expression of tyrosine hydroxylase (TH), vesicle monoamine transporter 2 (VMAT2), and α-synuclein, by using qPCR and Western blot techniques. Moreover, we quantified the effect of NAC on total dopamine levels using a dopamine ELISA assay.Results: Our results indicate that NAC has a neuroprotective role in SH-SY5Y cells exposed to 6-OHDA by maintaining cell proliferation and decreasing apoptosis. Additionally, we demonstrated that NAC treatment increases dopamine release and protects SH-SY5Y cells against 6-OHDA dysregulations on the proteins TH, VMAT2, and α-synuclein.Conclusions: Our findings contribute to the validation of compounds capable to restore dopamine homeostasis and shed light on the metabolic pathways that could be targeted to normalize dopamine turnover. Furthermore, our results highlight the effectiveness of the antioxidant NAC in the prevention of dopaminergic neurodegeneration in the present model.
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| 5. |
- Elf, Kristin, et al.
(författare)
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Temperature disturbances in traumatic brain injury : relationship to secondary insults, barbiturate treatment and outcome
- 2008
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Ingår i: Neurological Research. - 0161-6412 .- 1743-1328. ; 30:10, s. 1097-1105
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the occurrence of spontaneous hyper- and hypothermia in patients with traumatic brain injury using a computerized data collecting system, to show how temperature correlates with other secondary insults, to describe how temperature affects outcome and to show how barbiturate treatment influences those analyses. Methods: Patients with >= 54 hours of valid monitoring within the first 120 hours after trauma (one value/min) for temperature, intracranial pressure, cerebral perfusion pressure, systolic blood pressure, mean blood pressure and heart rate were included. Correlation analyses were performed between temperature and other secondary insult variables. The non-linear relationship between temperature and outcome (measured by Glasgow outcome scale 6 months post-trauma) was illustrated using a neural network. Results: Of the 53 patients, 44 experienced hyperthermia (>38 degrees C) and 29 experienced hypothermia (<36 degrees C). Hyperthermia correlated with occurrence of high blood pressure and high CPP. In individuals, hyperthermia also correlated with ICP and tachycardia. There was a trend towards better outcome for patients with normal temperature than those with hyper- or hypothermia (favorable outcome 64% versus 29 and 33% respectively). When patients treated with barbiturates were excluded, 60% showed favorable outcome in the hypothermia group as well. Barbiturate treatment also confounded analyses regarding temperature and other secondary insults. Discussion: Patients with hyperthermia, hypertension, high CPP and tachycardia may suffer from a hyperdynamic state. This may worsen outcome and hence clinical awareness is important. Barbiturate treatment confounds several analyses which have not been shown before. We recommend those patients to be analysed separately in future studies.
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| 6. |
- Eriksson, Ola, 1967-, et al.
(författare)
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In vitro evaluation of brain lesioning electrodes (Leksell) using a computer-assisted video system
- 1999
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Ingår i: Neurological Research. - 0161-6412 .- 1743-1328. ; 21:1, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- Radiofrequency (RF) generated thermal brain lesions are widely used in functional neurosurgery. The size, shape and development of the lesions depends on system parameter settings and the electrode configuration. Difficulties in studying the effect of these factors in vivo stimulated us to develop an in vitro system for standardized comparison between different electrodes and physical parameters. A computer-assisted video system was set-up allowing continuous video recording of RF-generated coagulations in either a standard albumin solution or in the fresh white of a hen's egg as transparent test substrates. Ten lesions were made with each test electrode (two bipolar and three monopolar) in each of the two substrates at 70 degrees, 80 degrees and 90 degrees C (t = 60 sec). Due to the better homogeneity the lesions in the albumin solution were much more regular and reproducible. This made it possible to calculate the size (width 2.2 +/- 0.1 to 5.3 +/- 0.1 mm and length 3.0 +/- 0.1 to 8.7 +/- 0.3 mm) as well as the volume (8.5 +/- 1.4 mm3 to 133.5 +/- 26.8 mm3). It is concluded that this in vitro system offers a reproducible way to study and document the effect of different electrode configurations and RF-generator settings on the formation of a heat lesion. Even if the results are not directly applicable to the living human brain they give an estimate of the form and size of a coagulation lesion and can be of value for standardized comparisons between different electrodes.
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| 7. |
- Gati, Istvan, et al.
(författare)
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Culturing of diagnostic muscle biopsies as spheroid-like structures: a pilot study of morphology and viability
- 2010
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Ingår i: Neurological Research. - : Forefront Publishing Group. - 0161-6412 .- 1743-1328. ; 32:6, s. 650-655
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to establish three-dimensional cultures originating from muscle biopsies and evaluate the viability and morphology. Method: Muscle biopsies from patients with suspected neuromuscular disorders were obtained and established as primary muscle tissue cultures. Tissue pieces, 1-2 mm of diameters, were placed in culture medium and subjected to sporadic stirring to prevent attachment and outgrowth as monolayer cells. Morphology and ability to attach to the surface were investigated by light microscopy. Viability was evaluated by Tc-99m-tetrofosmin uptake. After 1 month, histology was evaluated by light microscopy and immunocytochemistry. The findings of a healthy muscle and a dystrophic muscle were compared. Results: Initially, the tissue pieces were unshaped but formed spheroid-like structures during the culture period. For dystrophic muscle, attachment capacity to the surface was initially potent and decreased during the culture period, whereas control muscle showed weak attachment from the start that increased during the culture period. The uptake of Tc-99m-tetrofosmin increased in control muscle, while it decreased in dystrophic muscle, during the culture period. The histological investigation demonstrated larger destruction of myofiber, weaker satellite cell activation and reduced myofiber regeneration in the dystrophic muscle as compared to the control muscle. Conclusion: The cellular components of the muscle tissue can survive and proliferate as spheroid-like primary cultures. The cellular composition resembles the in vivo condition, which allows studies of degeneration of the original fibers, and activation and proliferation of the satellite cells. The culture system may provide better understanding of the degeneration and regeneration processes in different muscle disorders and allow investigations of pharmacological interventions.
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| 8. |
- Hart, Andrew M, et al.
(författare)
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Neuronal death after peripheral nerve injury and experimental strategies for neuroprotection.
- 2008
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Ingår i: Neurological Research. - 0161-6412 .- 1743-1328. ; 30:10, s. 999-1011
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Despite considerable microsurgical innovation in peripheral nerve repair, the outcome has improved little since the 1940s, reflecting surgical inability to adequately address the complex neurobiology of nerve injury and regeneration. Axotomy-induced neuronal death is potentially the most fundamental problem, and given recently published data, a review is timely. METHODS: Initial review of relevant doctoral theses from the University of Umeå, and Blond-McIndoe Research Laboratories, the University of Manchester, plus initial PubMed search including terms 'neuron death' and 'neuroprotection', subsequently expanded to relevant quoted articles. RESULTS: Various factors related to patient (principally age) and injury (Sunderland grade, proximity to cell body and mechanism) determine the extent of neuronal death, the mechanism of which is reviewed. A considerable proportion of sensory neurons (particularly small cutaneous afferents) die after distal injury and death is more widespread after proximal injury. Motor neurons are susceptible to post-ganglionic plexus and spinal root level injury. Root avulsion causes the greatest cell death. The time course of neuronal death is fortuitously slow and mainly occurs by a process akin to apoptosis. A therapeutic window therefore exists, as do potential neuroprotective targets. Nerve repair is partly neuroprotective, but must be performed early. Exogenous neurotrophic factor administration (e.g. in tissue engineered conduits) is beneficial, but not practical for various reasons. In contrast, adjuvant neuroprotective pharmacotherapy is practical, and two clinically safe agents are reviewed. Acetyl-L-carnitine arrests sensory neuronal death and speeds up regeneration. N-acetyl-cysteine provides comparable sensory neuronal protection via mitochondrial preservation and protects motor neurons. Both agents are well characterized experimentally and highly effective even after clinically relevant delays between injury and treatment. Barriers to translational research are being addressed. DISCUSSION: The future of peripheral nerve repair lies in modulating neurobiology at the time of injury, repair and during regeneration. Neuroprotection may be an essential component of that therapeutic package.
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| 9. |
- Holtz, A, et al.
(författare)
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Efficacy of the 21-aminosteroid U74006F in improving neurological recovery after spinal cord injury in rats.
- 1992
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Ingår i: Neurological Research. - 0161-6412 .- 1743-1328. ; 14:1, s. 49-52
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of three different regimens of the 21-aminosteroid U74006F in counteracting the neurological damage after spinal cord compression causing paraparesis in rats was investigated. Three groups of ten animals each were given totally 6 mg/kg of U74006F in different regimens beginning one hour after injury (A: bolus doses of 1.5 mg/kg at 1, 4, 7 and 10 hours; B: bolus of 1.5 mg/kg at 1 hour and 4.5 mg/kg as an infusion over the next 9 hours; and C: infusion alone, 6 mg/kg, given between 1 and 10 hours after trauma). Two groups of ten animals each received vehicle alone in administration modes comparable to those of the U74006F treated animals. The motor function was assessed daily on the inclined plane. On day one, the capacity angle had decreased from about 62 degrees preoperatively to 28-30 degrees in the two vehicle-treated groups and in group C. In these groups there was a similar improvement in neurological function and on day 9 the capacity angles were 49-55 degrees. In groups A and B, both of which received a bolus dose of U74006F at 1 hour, the neurological outcome improved on day one with capacity angles of 38-40 degrees. The difference in neurological function between the animals given U74006F as bolus doses and those given vehicle alone persisted over the entire observation span until day 9. The data suggest that early treatment with a bolus dose seems to be required in order to obtain an effect of U74006F on neurological recovery.
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| 10. |
- Lindvall-Axelsson, M, et al.
(författare)
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Actions of sex steroids and corticosteroids on rabbit choroid plexus as shown by changes in transport capacity and rate of cerebrospinal fluid formation
- 1990
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Ingår i: Neurological Research. - 0161-6412. ; 12:3, s. 181-186
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Tidskriftsartikel (refereegranskat)abstract
- The effect of betamethasone on choroid plexus transport and CSF formation in rabbits was studied. Following 5 days of daily treatment with betamethasone the CSF production rate was reduced by 43% as measured by ventriculo-cisternal perfusion with radioactive inulin. Accordingly, the Na(+)-K(+)-ATPase activity and the transport capacity in the choroid plexus, measured in terms of choline (10(-5) M) uptake and accumulation in vitro, decreased (in the lateral ventricles by 31% in both cases). Isolated choroid plexuses from rabbits were also used to determine uptake and accumulation of choline and the activities of various types of ATPases following pretreatment of the animals with 17-beta-oestradiol, alone or in combination with progesterone. The combined treatment reduced the choline uptake by 35% and also lowered the activity of Na(+)-K(+)-ATPase by 31% without influencing tissue wet weight. Thus, the demonstrated influences of glucocorticoids and sex steroids on the transport capacity in the choroid plexus seem to be important components in their postulated effects on intracranial hypertension.
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