Neuroprotective Effects of Trolox, Human Chorionic Gonadotropin, and Carnosic Acid on Hippocampal Neurodegeneration After Ischemiareperfusion Injury

Abstract

Introduction: One of the serious complications of stroke is memory impairment, which is considered as one of the complications of reperfusion of tissue. The present study was designed to compare the effect of administration of Trolox, carnosic acid and Human Chorionic Gonadotropin (HCG) immediately after reperfusion of the stroke tissue on the memory and hippocampal histology. Method: Ischemia-Reperfusion Model (IRI) was created by bilateral occlusion of the common carotid artery for 15 minutes and the first dose was administered immediately after reperfusion. 10 days after ischemia, passive avoidance memory test and apoptotic protein levels were evaluated. Results: Cerebral Ischemia perfusion reduced the time of latency in entering the dark box in the ischemic group. Administration of Trolox and HCG increased this latency time, while treatment with carnosic acid had no effect. Also, IRI significantly reduced the number of healthy cells in the hippocampus. Administration of Trolox, carnosic acid and HCG increased the number of healthy cells and decreased the expression of Caspase-3 and Bax, but significantly increased the expression of Bcl-2 compared to the ischemic group. Conclusion: Findings indicate the beneficial effects of HCG and Trolox on the improvement of memory and the number of healthy cells in the hippocampal region. It is worth noting that the amount of apoptosis in the hippocampus was significantly reduced by Trolox, HCG and Carnosic acid.

Hypogonadism induced by surgical stress and brain trauma is reversed by human chorionic gonadotropin in male rats: A potential therapy for surgical and TBI‐induced hypogonadism?

“…hCG is a safe, cheap, FDA‐approved treatment for hypogonadism in men (chronically), infertility in men and women, and to promote the descent of testicles in young boys with cryptorchidism 99 . In this context, hCG treatment has recently been shown to be effective in (1) raising plasma T concentrations in healthy men with chronic spinal cord injury, and this was not significantly different from hCG’s elevation of plasma T in able‐bodied male control subjects, 100 (2) protecting the rodent adult 37,38 and neonatal brain from hypoxic‐ischaemic cellular degeneration in vivo and inhibiting glutamate‐dependent excitotoxic or necrotic neuronal cell death in vitro 40 ; and (3) increasing ERK phosphorylation, neurite outgrowth and rescuing ovariectomy‐induced spatial memory deficits in C57Bl/6J mice 64 . In addition, hCG also partially attenuated hypoadrenalism in male rats.…”

“…protecting the rodent adult 37,38 and neonatal brain from hypoxicischaemic cellular degeneration in vivo and inhibiting glutamatedependent excitotoxic or necrotic neuronal cell death in vitro 40 ; and…”

“…Importantly, hCG has been shown to improve functional recovery following spinal cord injury in rats, 30,36,37 and decrease ischaemic brain injury in adult and neonatal rodent models of stroke. [38][39][40] Aside from these neuroprotectant properties, hCG also promotes neurite sprouting and neuron survival. 40 TBI-induced HH is thought to result from damage to the hypothalamus or pituitary 41,42 and/or stress-induced cortisol-mediated suppression of the HPG axis.…”

“…HH could therefore greatly compromise cognitive performance and neuroregeneration following a TBI. Importantly, hCG has been shown to improve functional recovery following spinal cord injury in rats, 30,36,37 and decrease ischaemic brain injury in adult and neonatal rodent models of stroke 38–40 . Aside from these neuroprotectant properties, hCG also promotes neurite sprouting and neuron survival 40 …”

Carnosic acid ameliorates depressive‐like symptoms along with the modulation of FGF9 in the hippocampus of middle carotid artery occlusion‐induced Sprague Dawley rats

“…Recently, carnosic acid has demonstrated neuro‐protection by decreasing the apoptosis in the hippocampus of the cerebral ischemic reperfusion model. Though, the effect of carnosic acid on post‐stroke depression‐like behavior was not studied (Babahajian et al, 2019). In present study, stroke model was established to study the possible effect of hypothesized pharmacological intervention against the post‐stroke depression‐like behavior.…”