uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Mechanisms of traumatic brain injury in the rat: Morphological consequences and neurotrophic responses
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Traumatic brain injury is a major cause of death and disability in the Western world. especially in young people. Understanding the pathophysiology of traumatic brain injury is the basis for further development of better therapeutic strategies for such patients. In this thesis the morphological consequences, behavioral outcome and neurotrophic responses are described in a rat model of cerebral cortical contusion injury produced by the weight drop technique. Axonal and dendritic injury were studied with APP and MAP2 immunohistochemistry; spontaneous motor activity and habituation in activity chambers; the expression of neurotrophic factors with mRNA in situ hybridization for bone morphogenetic protein receptors (ActR-I, ActR-IB, ActR-II, and BMPR-II), BDNF, trkB, pituitary adenylate cyclase activating polypeptide (PACAP) and its type 1 receptor (PACAP-R1), as well as apoptosis with TUNEL-staining and general morphology.

One and there days after injury there were accumulations of APP in axonal profiles in the subcortical white matter and in the ipsilateral thalamus, indicating disturbed axonal transport in regions close and remote to the cortical lesion. At this time there was loss of MAP2 immunoreactivity in the cortex in 50% of the animals and in the ipsilateral dentate hilus in all animals, indicating dendrosomatic lesions. Three weeks after injury there were still APP and MAP2 alterations, but less pronounced. Traumatized animals showed a hyperactive spontaneous motor behavior and a reduced ability for habituation to a new environment 16-18 days after injury. This functional impairment was attenuated in rats treated with the NMDA-receptor antagonist MK-801. There was no corresponding morphological correlate to the observed MK-801 effect on behavior. There was a cooperative upregulation of ActR-I and BMPR-II mRNAs at 6h in the ipsilateral dentate gyms suggesting a role for bone morphogenetic proteins (BMPs) in the plasticity of the injured brain. There was a rapid upregulation of BDNF mRNA in the ipsilateral cortex and dentate gyrus, with a concomitant upregulation of trkB in the dentate gurus peaking at 2h. PACAP mRNA was upregulated in the perimeter of the cortical lesion 72h after injury. PACAP-R1 mRNA was downregulated at 6h in the ipsilateral dentate gyrus. Maximal cell death and apoptosis were observed in the cortex 12-24h after injury. These findings suggest a role for PACAP in counteracting neuronal cell death after brain trauma. Pretreatment with the oxygen free radical spin trap PBN induced more apoptosis and a more rapid and less pronounced PACAP response in treated animals, suggesting a role for free radicals in regulating posttraumatic PACAP gene expression and programmed cell death.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1998. , 57 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 796
Keyword [en]
Neurosciences, Cortical contusion injury, TBI, neurons, axons, dendrites, APP, MAP2, BMPR-II, ActR-I, trkB, c-fos, BDNF, PACAP, TUNEL, TGFs, serine/threonine, bone morphogenetic protein, neuropeptides, reactive oxygen species, ROS, apoptosis
Keyword [sv]
National Category
Research subject
URN: urn:nbn:se:uu:diva-232ISBN: 91-554-4328-1OAI: oai:DiVA.org:uu-232DiVA: diva2:161842
Public defence
1998-12-11, Grönwallsalen,University Hospital, Entrance 70, Uppsala, Uppsala, 13:15
Available from: 1998-11-20 Created: 1998-11-20Bibliographically approved

Open Access in DiVA

No full text
Buy this publication >>

By organisation
Department of Neuroscience

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 179 hits
ReferencesLink to record
Permanent link

Direct link