Abstract
Traumatic brain injury (TBI) often causes a persistent and debilitating impairment of cognitive function. Although the neurochemical basis for TBI-induced cognitive dysfunction is not well characterized, some studies suggest prominent involvement of the CNS cholinergic system. Previous studies from our laboratories have shown that α7* nicotinic cholinergic receptors (nAChrs) are especially vulnerable to the pathophysiological effects of TBI. Hippocampal and cortical α-[125I]-bungarotoxin (BTX) expression of α7* nAChrs is significantly decreased in many brain regions following TBI and this reduction persists for at least 3 weeks following injury. In the present study we evaluated whether chronic nicotine infusion could attenuate TBI-induced deficits in α7* nAChr expression. Male Sprague-Dawley rats were sham-operated, or subjected to mild or moderate unilateral cortical contusion injury. Immediately following brain injury, osmotic mini-pumps that delivered chronic saline or nicotine (0.125 or 0.25 mg/kg/h) were implanted. The animals were euthanatized and the brains prepared for nAChr quantitative autoradiography, 7 days following surgery. Brain injury caused significant decreases in BTX binding in several regions of the hippocampus. TBI-induced deficits in α7* nAChr density were reversed in four of the six hippocampal brain regions evaluated following chronic nicotine administration. If TBI-induced deficits in α7* nAChr expression play a role in post-injury cognitive impairment, pharmacological treatments which restore nAChr binding to control levels may be therapeutically useful.
Original language | English |
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Pages (from-to) | 224-233 |
Number of pages | 10 |
Journal | Neuropharmacology |
Volume | 44 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2003 |
Bibliographical note
Funding Information:These studies were funded by grants from the Kentucky Spinal Cord and Head Injury Research Trust (KySCHIRT), the University of Kentucky Chandler Medical Center Research Foundation and the National Institutes of Health (NS39828 to SWS and NS42196 to JRP).
Keywords
- Bungarotoxin
- Cholinergic
- Nicotine
- Nicotinic receptors
- Traumatic brain injury
- α7
ASJC Scopus subject areas
- Pharmacology
- Cellular and Molecular Neuroscience