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Removing the barriers of plasticity after experimental brain injury
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- Christensen, Jakob Hakon (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
- (creator_code:org_t)
- ISBN 9789176195925
- 2018
- English 66 s.
- Doctoral thesis (other academic/artistic)
Abstract
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- Ischemic stroke and traumatic brain injuries (TBI) are leading causes of disability and death worldwide. Both injuries result in regional cell death and disruption of local and remote functional neuronal networks, leading to loss of neurological function. Despite much effort spent on developing pharmacological therapies to reduce neuronal damage following these conditions, no neuroprotective strategies have reached clinical use. Spontaneous recovery of lost function after stroke and TBI is limited but can be enhanced by rehabilitative strategies that stimulate experience-driven brain plasticity.In the experimental setting, exposure to multimodal stimulation by enriched environments (EE) stimulates brain plasticity and recovery following brain injuries. At the system level, we demonstrated that improvement of tactile- proprioceptive function following rehabilitation in EE was associated with enhanced functional-connectivity among distinct brain regions involved in integration of multisensory input and control of movement. Inhibition of the metabotropic glutamate receptor 5 (mGluR5) and genetic disruption of peri- neuronal nets facilitated remodeling of resting-state networks within contralesional cortical sensorimotor areas during stroke recovery. Using the EE regime, we identified several molecular barriers, which appear to impair functional recovery and plasticity in the first weeks following stroke and TBI. These included peri- lesional inflammation, parvalbumin expressing GABAergic inhibitory interneurons and aberrant mGluR5 activation.Overall this thesis presents novel data regarding molecular and network level mechanisms of plasticity, and provide potential targets for future therapies, which may support rehabilitation of patients following matured brain injury.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Resting-state functional connectivity, Optical imaging, Stroke, Recovery, Enriched environment, Parvalbumin, Perineuronal nets, Traumatic brain injury, Microglia.
Publication and Content Type
- dok (subject category)
- vet (subject category)
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