In vivo evaluation of a chronic treatment with a 5-HT2 agonist on visual impairment in a mouse model of stroke: a pilot study

Stroke is a disease caused by poor blood flow to the brain that results in neuronal cells death. The lack of blood flow is known as ischemic stroke, as opposed to the haemorrhagic stroke. Stroke is the second-leading cause of the death worldwide and the major cause of disability. 12.2 million of stroke cases were reported in 2019, with 7.3 million being ischemic stroke. Signs and symptoms often appear soon after the stroke has occurred and depend on the affected area. When the ischemic stroke hit the visual cortex, defects of various severity in the visual field are likely to occur. Anticoagulant medicines or surgical procedures, together with rehabilitation, are part of the usual treatment of ischemic stroke. Nevertheless, none of these options is specific for one symptom. Therefore, in this study, our aim is to explore a possible treatment to improve visual deficits consequent to an ischemic stroke. Thus, we induced in mice (C57/B6J) an ischemic stroke at the level of the V1 area using the photothrombotic model. Following the ischemic stroke, we treated for 30 days a group of animals with vehicle (control group) and another group with a 5-HT2 receptor agonist. Serotonin is known to have an important neuromodulatory action by activating its different receptors subtypes, among which 5-HT2 agonists are supposed to stimulate the neurogenesis of dendritic spines. We hypothesized that this neuroplastic effect could be beneficial in treating the consequences of an ischemic stroke in the visual cortex. Visual abilities of the mice were assessed using behavioural pharmacology tests, to evaluate motor coordination, learning, and spatial memory that may have been compromised due to the impaired vision. Our preliminary results showed a tendency of mice treated with the 5-HT2 agonist to perform better in some of the behavioural tests, compared with control mice. We observed a better performance, measured as higher % of alternations between arms, in the T-maze test made in absence/scarce conditions of light (using an infrared light). We also found a greater index of learning in the Cued Morris Water maze test, and a higher time spent in the “shallow” zone of the Visual Cliff in mice treated with the 5-HT2 agonist than with vehicle. After the behavioural testing we performed histological verification of the lesioned brain area in the two groups. No differences were observed in the lesioned area comparing controls and treated mice. Possible effects of the 5-HT2 agonist on neuroplasticity will be determined using the Thy-1-GFP M mouse model which constitutively express a green fluorescent protein under the Thy1 gene promoter in the brain. This pilot study indicates that treatment with 5-HT2 agonists may lead to an improvement of visual abilities after an ischemic stroke at the level of the visual cortex.