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Cerebrolysin reduces blood-cerebrospinal fluid barrier permeability change, brain pathology, and functional deficits following traumatic brain injury in the rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2010 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1199, 125-137 p.Article in journal (Refereed) Published
Abstract [en]

Traumatic brain injuries (TBIs) induce profound breakdown of the blood-brain and blood-cerebrospinal fluid barriers (BCSFB), brain pathology/edema, and sensory-motor disturbances. Because neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and glial cell-derived neurotrophic factor (GDNF), are neuroprotective in models of brain and spinal cord injuries, we hypothesized that a combination of neurotrophic factors would enhance neuroprotective efficacy. In the present investigation, we examined the effects of Cerebrolysin, a mixture of different neurotrophic factors (Ebewe Neuro Pharma, Austria) on the brain pathology and functional outcome in a rat model of TBI. TBI was produced under Equithesin (3 mL/kg, i.p.) anesthesia by making a longitudinal incision into the right parietal cerebral cortex. Untreated injured rats developed profound disruption of the blood-brain barrier (BBB) to proteins, edema/cell injury, and marked sensory-motor dysfunctions on rota-rod and grid-walking tests at 5 h TBI. Intracerebroventricular administration of Cerebrolysin (10 or 30 mu L) either 5 min or 1 h after TBI significantly reduced leakage of Evans blue and radioiodine tracers across the BBB and BCSFB, and attenuated brain edema formation/neuronal damage in the cortex as well as underlying subcortical regions. Cerebrolysin-treated animals also had improved sensory-motor functions. However, administration of Cerebrolysin 2 h after TBI did not affect these parameters significantly. These observations in TBI demonstrate that early intervention with Cerebrolysin reduces BBB and BCSFB permeability changes, attenuates brain pathology and brain edema, and mitigates functional deficits. Taken together, our observations suggest that Cerebrolysin has potential therapeutic value in TBI.

Place, publisher, year, edition, pages
2010. Vol. 1199, 125-137 p.
Keyword [en]
traumatic brain injury, brain edema, blood-brain barrier, blood-CSF barrier, choroid plexus, neuronal injury, cell death, Cerebrolysin, intracerebroventricular administration, sensory-motor function
National Category
Anesthesiology and Intensive Care
URN: urn:nbn:se:uu:diva-136481DOI: 10.1111/j.1749-6632.2009.05329.xISI: 000282838900015OAI: oai:DiVA.org:uu-136481DiVA: diva2:377571
Available from: 2010-12-14 Created: 2010-12-13 Last updated: 2012-03-15Bibliographically approved

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Sharma, Hari Shanker
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