Neuropharmacological assessment of intrathecal thyrotropin-releasing hormone in cerebral ischemia

Background: In experimental models of central nervous system damage, thyrotropin-releasing hormone (TRH) has been shown to have neuromodulatory, antioxidant and anti-inflammatory effects. Its neuroprotective efficacy in embolic cerebral ischemia remains unknown. Objectives: This study evaluated the effects of intrathecal TRH administration on cerebral infarct volume, oxidative stress and inflammatory markers in a rabbit model of embolic cerebral ischemia. Methods: Twenty adult female New Zealand white rabbits were randomly divided into two groups (n = 10 per group): a control group and a TRH-treated group. Injecting broken autologous blood clots into the right common carotid artery caused cerebral ischemia. Forty-five minutes after embolization, the treatment group received intrathecal TRH (0.20 mg/kg) via the cisterna magna. Serum interleukin-1? (IL-1?) concentrations and levels of lactate and malondialdehyde (MDA) in the cerebrospinal fluid (CSF) were assessed at baseline and 24 hours after embolization. Computerized histopathological image analysis was used to measure the volume of the cerebral infarct. Results: The mean cerebral infarct volumes at 24 hours varied slightly between the TRH-treated group (122.84 ± 15.84 mm³) and the control group (126.79 ± 14.04 mm³) (p = 0.496). Serum levels of IL-1?, MDA and CSF lactate increased statistically significantly (p <.05) in both the TRH-treated and control groups. Following embolization, the TRH-treated group had decreased serum levels of CSF lactate, CSF MDA and IL-1?; nevertheless, none of the group comparisons were significant (p >.05). Conclusion: Although no statistically significant differences were observed, consistent directional reductions in infarct volume and biochemical markers suggest potential biological activity of TRH that may require optimization of dosing and study design. At the dosage and duration employed in this study, TRH showed limited efficacy under the experimental conditions.