Electric Stimulation of Neurogenesis Improves Behavioral Recovery After Focal Ischemia in Aged Rats

Abstract

The major aim of stroke therapies is to stimulate brain repair and to improve behavioral recuperation after cerebral ischemia. Despite remarkable advances in cell therapy for stroke, stem cell-based tissue replacement has not been achieved yet stimulating the search for alternative strategies for brain self-repair using the neurogenic zones of the brain, the dentate gyrus and the subventricular zone (SVZ). However, during aging, the potential of the hippocampus and the SVZ to generate new neuronal precursors, declines. We hypothesized that electrically stimulation of endogenous neurogenesis in aged rats could increase the odds of brain self-repair and improve behavioral recuperation after focal ischemia. Following stroke in aged animals, the rats were subjected to two sessions of electrical non-convulsive stimulation using ear-clip electrodes, at 7- and 24 days after MCAO. Animal were sacrificed after 48 days. We report that electrical stimulation (ES) stimulation of post-stroke aged rats led to an improved functional recovery of spatial long-term memory (T-maze) but not on the rotating pole or the inclined plane, both tests requiring complex sensorimotor skills. Surprisingly, ES had a detrimental effect on the asymmetric sensorimotor deficit. Histologically, there was a robust increase in the number of doublecortin-positive cells in the dentate gyrus and SVZ of the infarcted hemisphere and the presence of a considerable number of neurons expressing tubulin beta III in the infarcted area. Among the gene that were unique to ES, we noted increases in the expression of seizure related 6 homolog like which is one of the physiological substrate of the β-secretase BACE1 involved in the pathophysiology of the Alzheimer’s disease and Igfbp3 and BDNF receptor mRNAs which has been shown to have a neuroprotective effect after cerebral ischemia. However, ES was associated with a long-term down regulation of cortical gene expression after stroke in aged rats suggesting that gene expression in the peri-infarcted cortical area may not be related to electrical stimulation induced-neurogenesis in the subventricular zone and hippocampus.

Electroacupuncture Promoted Nerve Repair After Peripheral Nerve Injury by Regulating miR-1b and Its Target Brain-Derived Neurotrophic Factor

“…Due to differences in structure and function, damaged axons in the central nervous system (CNS) of adult mammals are usually unable to regenerate, while nerve recovery is generally very poor despite the ability of peripheral nerves to spontaneously regenerate after PNI ( Gu et al, 2014 ). Both electrical stimulation ( Balseanu et al, 2020 ; Wu et al, 2020 ) and acupuncture ( Wong et al, 2011 ; He et al, 2015 ) have beneficial effects on PNI ( He et al, 2015 ; Wu et al, 2020 ) or central nerve injury (CNI) ( Wong et al, 2011 ; Balseanu et al, 2020 ). EA, which is the combination of electrical stimulation and acupuncture, has therapeutic effects on both PNI ( Wu J. et al, 2018 ) and CNI ( Cai et al, 2020 ).…”

Improved Functional Outcome After Peripheral Nerve Stimulation of the Impaired Forelimb Post-stroke

“…Using this model, these trophic factors, and others, should be assayed to determine if changes in their levels could potentially correlate with both function and midline crossing. (4) Peripheral nerve stimulation has recently been shown to lead to subventricular zone (SVZ) neurogenesis (72), which has been implicated as a source of migrating neural progenitors to the lesioned motor cortex (73). Taken together, these possible mechanisms suggest that the neuroplastic effects promoted by peripheral nerve stimulation may not only act locally, but also likely involve multiple pathways and cellular mechanisms.…”

Stimulation of the Migration and Expansion of Adult Mouse Neural Stem Cells by the FPR2-Specific Peptide WKYMVm

“…The therapeutic candidates and technologies, including drugs and stem cells, to treat damaged brain and epilepsy and to restore nerve cells are being studied for clinical application [55][56][57]. Despite advances in cell therapy in regenerative medicine, stem cellbased replacement therapy has drawbacks such as its low cell yield, low transplantation rate, high costs, and low safety [58,59].…”