Effect of testosterone on functional recovery in a castrate male rat stroke model

• Published in: Brain research 2005-05, Vol.1043 (1), p.195-204
• Main Authors: Pan, Yi, Zhang, Haibo, Acharya, Aninda B., Patrick, Ping H., Oliver, Dana, Morley, John E.
• Format: Article
• Language: English
• Subjects: Androgens - pharmacology; Animals; Axons - metabolism; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cerebral Cortex - pathology; Cerebral Cortex - physiology; Functional recovery; GAP-43 Protein - metabolism; GFAP; Immunohistochemistry; Male; Medical sciences; Motor Activity - drug effects; Nerve Regeneration - drug effects; Neurology; Neurons, Afferent - physiology; Orchiectomy; Rat; Rats; Rats, Sprague-Dawley; Recovery of Function - drug effects; Stroke; Stroke - drug therapy; Stroke - pathology; Stroke - physiopathology; Synaptophysin - metabolism; Testosterone; Testosterone - pharmacology; Touch - drug effects; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2005.02.078

Both increased and decreased testosterone levels have been reported to correlate with poor outcome after acute ischemic stroke. The present study focused on the role of testosterone during recovery from neurological deficits in a rat focal ischemia model. Castrate male rats were subjected to behavioral tests after 90 min of middle cerebral artery occlusion (MCAO). On day 7 post-MCAO, neurological deficit-matched rats were assigned to a treatment group implanted with subcutaneous testosterone pellets or a control group implanted with sham cholesterol pellets. After 4 weeks post-MCAO, the average infarct volume was not significantly different between the two groups. Rats in the testosterone group demonstrated significantly earlier improvement in neurological deficits and shortened latency of adhesive tape removal compared with the control group as analyzed by Wilcoxon signed ranks test. Walking on parallel bars improved in both groups with a trend towards early recovery observed in the testosterone group. Biased left body swings persisted during the test period in both groups post-MCAO. Serum testosterone was within physiological levels in the treatment group but was not detectable in the control group by radioimmunoassay. GAP-43 and synaptophysin expression did not differ between groups. Less GFAP expression and reactive astrocyte hypertrophy were found around the infarct area in testosterone-treated rats compared with control rats. In conclusion, testosterone replacement post-MCAO accelerated functional recovery in castrate rats, suggesting a potential therapeutic role for testosterone replacement in stroke recovery.