The Effect of Olanzapine through Antioxidant and Anti-Inflammation on the Hippocampus in the Asphyxial Cardiac Arrest Rat Model

Abstract

Introduction: Cardiac arrest (CA) often leads to severe brain damage, resulting in neurological disorders and high mortality rates. Hypothermia treatment (HT) is commonly used in clinical practice after CA/cardio-pulmonary resuscitation (CA/CPR) because it has been shown to improve neurological outcomes and increase survival rates. Olanzapine, a medication known to induce hypothermia, has not been extensively studied in the context of CA/CPR. This study aimed to investigate the neuroprotective effects and mechanisms of olanzapine-induced hypothermia (OIH) following ROSC. Male Sprague-Dawley rats were subjected to the following conditions: (i) Sham: no asphyxial CA + saline, (ii) CA: asphyxial CA + saline, and (iii) OCA: asphyxial CA + olanzapine treatment after the return of spontaneous circulation (ROSC). Result CA/CPR resulted in high mortality, severe neurological impairments, and hippocampal neuron damage observed after 5 days in the asphyxia CA group. These pathological complications were ameliorated by olanzapine treatment. OIH also protected the pyramidal neurons in the CA1 region of the hippocampus. The expression of antioxidant factors SOD-1, SOD-2, and CAT were upregulated in the olanzapine-treated group compared to the CA group. Moreover, olanzapine treatment following asphyxial CA reduced the expression of the pro-inflammatory factor COX-2 and the nuclear transcription factor NF-κB, which was sustained for up to 5 days compared to the CA group. OIH provides protection against cerebral injury following ROSC by enhancing the expression of antioxidant and anti-inflammatory factors. Conclusion The results of our study demonstrate that Olanzapine, an atypical antipsychotic medication, induces a noteworthy reduction in body temperature in the asphyxial CA rat model. The effectiveness of hypothermia treatment was evident by its antioxidant and anti-inflammatory mechanisms. Therefore, we suggest olanzapine as a promising therapeutic agent for alleviating cerebral injury via hypothermia in patients with CA.