Neuroscience 2000 Abstract
| Presentation Number: | 94.14 |
|---|---|
| Abstract Title: | Neuroprotection by dexanabinol following nerve agent-induced seizures: determination of the therapeutic window. |
| Authors: |
Ballough, G. P. H.*1
; Forster, J. S.2
; Jaworski, M. J.1
; Jaworski, J. M.1
; Filbert, M. G.2
1Dept of Biology, La Salle Univ, Philadelphia, PA 2Neurotoxicology, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD |
| Primary Theme and Topics |
J. Disorders of the Nervous System and Aging - 141. Neurotoxicity |
| Secondary Theme and Topics | J. Disorders of the Nervous System and Aging<br />- 134. Ischemia: neuroprotection and tolerance |
| Session: |
94. Neurotoxicity III Poster |
| Presentation Time: | Sunday, November 5, 2000 9:00 AM-10:00 AM |
| Location: | Hall G-J |
| Keywords: | Soman, neuroprotection, HU-211, seizures |
Recent findings by our laboratory have shown that dexanabinol (i.e, HU-211, Pharmos Ltd, Rehovot, Israel), a non-psychotropic derivative of THC, provides considerable neuroprotection against nerve agent (i.e., soman)-induced seizure-related brain damage (SRBD), when administered 5 min or 40 min following seizure onset. This neuroprotective effect is believed to result from dexanabinol’s dual action as a NMDA receptor antagonist and free radical scavenger. The present study was undertaken to further assess dexanabinol’s threapeutic window of effectiveness to alleviate soman-induced SRBD. Male Sprague-Dawley rats were challenged with 180 μ/kg soman (i.e., 1.6 LD50). They were subsequently given a single intraperitoneal injection of 25 mg/kg dexanabinol at either 1.5, 2, 4 or 6h post-seizure onset. HI-6 (125 mg/kg) and atropine methylnitrate (2 mg/kg) were administered to protect against the peripheral effects of soman. Electrocorticographic (EcoG) recordings were monitored via indwelling cortical electrodes. Rats were euthanatized 27h after soman administration. Alternate brain hemispheres were processed for microtubule-associated protein 2 (MAP2) immunohistochemistry or hematoxylin and eosin (H&E) histochemical staining. Morphometric image analysis was used to assess the cross-sectional areas of temporal lobe necrosis (MAP2-negative), and lesion volumes were determined from sequential serial sections. H&E-stained sections were examined for classical histopathology. All rats that received soman showed EcoG evidence of sustained seizures and status epilepticus for several hours. Consistent with our previous findings, dexanabinol had no apparent effect on the strength or duration of soman-induced seizures. However, the present findings also indicate that dexanabinol did not diminsh soman-induced SRBD when administered 1.5, 2, 4 or 6h following seizure onset. Taken together, our previous findings and those of the present study indicate that the neuroprotective efficacy of dexanabinol, to alleviate soman-induced SRBD, significantly attenuates at administration delays greater than 40min post-seizure onset. Future studies will examine possible neuroprotection synergy produced by co-administration of dexanabinol and anticonvulsant therapy.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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