Abstract
Purpose: In the present study we assessed the ability of BSF476921, an inhibitor of vascular endothelial growth factor receptor (VEGFR) kinase signal transduction, to reduce edema formation and neurologic motor dysfunction following lateral fluid percussion (FP) brain injury in rats. Methods: Anesthetized adult male rats were subjected to either lateral FP brain injury of moderate severity (n = 37) or sham injury (n = 22, surgery without brain injury). Animals were randomized to receive i.p. injections of either BSF476921 (30 mg/kg bw; injured n = 15, sham n = 11) or sterile water (injured n = 14, sham n = 11) at 1, 11 and 22 hours post-injury. After assessment of motor function using a standard 28-point neuroscore, animals were sacrificed 24 hours following trauma and their brains evaluated for regional water content using the wet-weight/dry-weight technique. Results: Although brain-injured animals showed a significant motor deficit compared to uninjured animals, no differences were detected between BSF476921- and vehicle-treated animals at the acute 24 hour post-injury time point. However, BSF476921 significantly attenuated regional edema formation in brain-injured animals in the ipsilateral hippocampus (p < 0.05) and in the cortex adjacent to the injury (p < 0.05) when compared to vehicle treatment. Conclusions: To our knowledge, this is the first report of a small molecule VEGFR kinase inhibitor reducing cerebral edema in a widely accepted model of brain injury.
| Original language | English |
|---|---|
| Pages (from-to) | 73-79 |
| Number of pages | 7 |
| Journal | Restorative Neurology and Neuroscience |
| Volume | 22 |
| Issue number | 2 |
| State | Published - 2004 |
Funding
These studies were supported, in part, by the BASF Bioresearch Corporation, grants from the National Institutes of Health (NIH) NINDS NS P50-08803, NS R01-40978, NIGMS GM RO1-34690, and a Veterans Administration Merit Review grant. PML was supported by a fellowship on NRSA T32 NS07413-04. Animal welfare guidelines as outlined by the Institutional Animal Care and Use Committee (IACUC) of the University of Pennsylvania were carefully adhered to in accordance with federal guidelines for the humane treatment of laboratory animals [33].
| Funders | Funder number |
|---|---|
| National Institutes of Health (NIH) | |
| U.S. Department of Veterans Affairs | |
| BASF Bioresearch Corporation | |
| Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | NS R01-40978, NS P50-08803 |
| National Institute of General Medical Sciences | GM RO1-34690 |
| Israel National Road Safety Authority | T32 NS07413-04 |
Keywords
- Blood brain-barrier
- Cerebral edema
- Head injury
- Neuromotor function
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience
- Clinical Neurology