An immunohistochemical analysis of the neuroprotective effects of memantine, hyperbaric oxygen therapy, and brimonidine after acute ischemia reperfusion injury

PURPOSE This study applies treatment methods to rat retinas subjected to acute ischemia reperfusion injury and compares the efficacy of memantine, hyperbaric oxygen (HBO) therapy, and brimonidine by histopathological examination. METHODS Thirty adult Wistar albino rats were divided into five groups after retinal ischemia was induced by elevating the intraocular pressure to 120 mmHg. The groups were as follows: group 1: control; group 2: acute retinal ischemia (ARI) model but without treatment group; group 3: memantine (MEM) treatment group; group 4: HBO therapy group; and group 5: brimonidine treatment (BRI) group. In the control group, right eyes were cannulated with a 30-gauge needle and removed without causing any intraocular pressure change. The ARI group was an acute retinal ischemia model, but without treatment. In the MEM group, animals were given a unique dose of intravenous 25 mg/kg memantine by the tail vein route after inducing ARI. In the HBO group, at 2 h following ARI, HBO treatment was applied for nine days. In the BRI group, a 0.15% brimonidine tartrate eye drop treatment was applied twice a day (BID) for seven days before ARI. Twenty-one days after establishing ischemia reperfusion, the right eyes were enucleated after the cardiac gluteraldehyde perfusion method, and then submitted to histological evaluation. RESULTS On average, the total retinal ganglion cell number was 239.93 ± 8.60 in the control group, 125.14 ± 7.18 in the ARI group, 215.89 ± 8.36 in the MEM group, 208.69 ± 2.05 in the HBO group, and 172.27 ± 8.16 in the BRI group. Mean apoptotic indexes in the groups were 1.1 ± 0.35%, 57.71 ± 0.58%, 23.57 ± 1.73%, 15.63 ± 0.58%, and 29.37 ± 2.55%, respectively. CONCLUSIONS The present study shows that memantine, HBO, and brimonidine therapies were effective in reducing the damage induced by acute ischemia reperfusion in the rat retina. Our study suggests that these treatments had beneficial effects due to neuroprotection, and therefore may be applied in clinical practice.