Neuroprotective effects of vincamine on cranial irradiation-induced cognitive impairment in mice

Introduction

The growing use of ionising radiation in diagnostic and therapeutic medicine has increased concern about injury to normal tissues, particularly the central nervous system. Radiation-induced cognitive and behavioural impairments may arise from oxidative stress, neurovascular dysfunction, neuroinflammation, and damage to neuronal precursor cells, leading to impaired neurogenesis, altered synaptic function, and deficits in learning and memory. Vincamine, owing to its cerebrovascular, antioxidant, anti-inflammatory, and neurometabolic properties, represents a potential neuroprotective agent for attenuating radiation-induced brain injury.

Aims

To evaluate the effect of vincamine on spatial learning, locomotor activity, exploratory behaviour, and anxiety-related responses after cranial irradiation.

Methods

Adult laboratory white mice were randomly assigned to three groups: control, cranial irradiation and cranial irradiation plus vincamine (n=10/group). Cranial irradiation was performed using a ¹³⁷Cs gamma irradiation system delivering a total cranial dose of 30 Gy at a dose rate of 1.1 Gy/min. Vincamine was administered subcutaneously three times weekly for two weeks, starting on the day of irradiation at 20 mg/kg, followed by 50 mg/kg for subsequent injections. Behavioural testing was conducted on days 2, 7, 14, and 21 after irradiation using the Morris water maze and open field test. Spatial learning was assessed by escape latency, swimming distance, and swimming velocity. Locomotor, exploratory, and anxiety-related behaviour were evaluated in the open field test. Behavioural tracking was performed using EthoVision XT 18 software.

Results

Cranial irradiation impaired Morris water maze performance, as shown by consistently prolonged escape latency and increased swimming distance compared with control animals. Escape latency was higher in irradiated mice at all assessed time points, increasing from 46±2 s on day 2 to 65±1.8 s on day 21, whereas control animals maintained shorter latencies. Vincamine treatment reduced escape latency in irradiated mice during the post-irradiation period. One-way analysis of variance demonstrated significant group effects for escape latency across all testing days. Irradiation also increased the swimming distance required to locate the platform, particularly on days 14 and 21, when irradiated mice travelled 870±16 cm and 910±18 cm, respectively. Vincamine reduced these distances to 588±16 cm and 288±18 cm, indicating improved spatial search efficiency. Swimming velocity varied across time points, suggesting that improvements in latency and distance were not attributed solely to locomotor changes. In the open field test, irradiated mice spent less time in the centre zone than controls, indicating increased anxiety-like behaviour and reduced exploratory activity. Vincamine partially restored centre-zone exploration, suggesting attenuation of radiation-induced anxiety-like behavioural responses.

Conclusions

Cranial irradiation produced persistent deficits in spatial navigation and anxiety-related exploratory behaviour. Vincamine-treated mice showed improved Morris water maze performance, reflected by shorter escape latency and reduced swimming distance compared with untreated irradiated animals. These effects were particularly evident on post-irradiation days 14 and 21, suggesting enhanced spatial navigation and partial recovery of hippocampus-dependent learning. Increased centre-zone exploration in the open field test further indicates reduced anxiety-like behaviour. These findings support further investigation of vincamine as a potential neuroprotective strategy for cranial irradiation-associated brain dysfunction.

References

No References