Brain Stimulation (Nov 2024)
Deep brain stimulation mitigates memory deficits in a rodent model of traumatic brain injury
Abstract
Background: Traumatic brain injury (TBI) is a major life-threatening event. In addition to neurological deficits, it can lead to long-term impairments in attention and memory. Deep brain stimulation (DBS) is an established therapy for movement disorders that has been recently investigated for memory improvement in various disorders. In models of TBI, stimulation delivered to different brain targets has been administered to rodents long after the injury with the objective of treating motor deficits, coordination and memory impairment. Objective: To test the hypothesis that DBS administered soon after TBI may prevent the development of memory deficits and exert neuroprotective effects. Methods: Male rats were implanted with DBS electrodes in the anterior nucleus of the thalamus (ANT) one week prior to lateral fluid percussion injury (FPI). Immediately after TBI, animals received active or sham stimulation for 6 h. Four days later, they were assessed in a novel object/novel location recognition test (NOR/NLR) and a Barnes maze paradigm. After the experiments, hippocampal cells were counted. Separate groups of animals were sacrificed at different timepoints after TBI to measure cytokines and brain derived neurotrophic factor (BDNF). In a second set of experiments, TBI-exposed animals receiving active or sham stimulation were injected with the tropomyosin receptor kinase B (TrkB) antagonist ANA-12, followed by behavioural testing. Results: Rats exposed to TBI given DBS had an improvement in several variables of the Barnes maze, but no significant improvements in NOR/NLR compared to Sham DBS TBI animals or non-implanted controls. Animals receiving stimulation had a significant increase in BDNF levels, as well as in hippocampal cell counts in the hilus, CA3 and CA1 regions. DBS failed to normalize the increased levels of TNFα and the proinflammatory cytokine IL1β in the perilesional cortex and the hippocampus of the TBI-exposed animals. Pharmacological experiments revealed that ANA-12 administered alongside DBS did not counter the memory improvement observed in ANT stimulated animals. Conclusions: DBS delivered immediately after TBI mitigated memory deficits, increased the expression of BDNF and the number of hippocampal cells in rats. Mechanisms for these effects were not related to an anti-inflammatory effect or mediated via TrkB receptors.
