Intranasal injection of recombinant human erythropoietin improves cognitive and visual impairments in chronic cerebral ischemia rats

The present study aimed to study the protective effect of intranasally delivered recombinant human erythropoietin (rhEPO) on cognitive and visual impairments in a permanent bilateral common carotid artery occlusion (2VO)-induced chronic cerebral ischemia (CCI) rat model. Male Sprague-Dawley rats (age, 6 months) with 2VO-induced CCI were treated with intranasal rhEPO (50 U/100 g) once per week for 8 weeks. A Morris water maze was used to evaluate the spatial learning and memory of the rats. Flash visual evoked potentials were measured to assess retinal function. Hematoxylin and eosin staining was performed to visualize and evaluate histopathological changes in the cerebral cortex, the hippocampus CA1 region and the retina. CCI-induced learning, memory and visual impairments were significantly alleviated in rats treated with rhEPO compared with those treated with a saline vehicle control. This was evidenced by remarkably decreased escape latency, increased frequency of crossing the hidden platform and elevated amplitude of primary wave in the rats treated with rhEPO. In addition, the rats experienced CCI-induced histopathological alterations, demonstrated by thinning of the cerebral cortex and retina, and losses of neurons and retinal ganglion cells. These alterations were significantly reversed in response to rhEPO administration compared with the saline vehicle control group. rhEPO may exert a protective role against cognitive and visual impairments in rats with CCI at least partially through preventing the thinning of the cerebral cortex and retina, as well as by inhibiting the loss of neurons and retinal ganglion cells.