The drug gabapentin may boost functional recovery after a stroke:

Gabapentin, which is presently used to control seizures and relieve nerve pain, may enable neurons on the uninjured side of the brain take up the signaling task of missing cells, according to new mice research.

The trials were designed to simulate an ischemic stroke in humans, which occurs when a clot stops blood flow and neurons die in the afflicted brain area.

Daily gabapentin therapy for six weeks after a stroke recovered fine motor capabilities in the animals’ upper limbs, according to the findings. The researchers discovered that functional improvement remained even after therapy was discontinued.

The Ohio State University researchers previously discovered that gabapentin inhibits the function of a protein that, when produced at high levels following a brain or spinal cord damage, inhibits the regrowth of axons, the long, thin projections of nerve cell bodies that convey signals.

“When this protein levels are high, it interferes with neurological recovery,” said lead author Andrea Tedeschi, an assistant professor of neurology in the College of Medicine at Ohio State.

“Think of this protein as the brake pedal and recovery as the gas pedal.” “You may press the gas pedal but not accelerate as long as you also press the brake pedal,” Tedeschi explained. “You can dramatically speed up recovery if you start raising the brake pedal and continually pressing on the throttle.” We believe that is the impact of gabapentin on neurons, with non-neuronal cells contributing to this process and making it even more effective.”

The work was published in the journal Brain on May 23, 2022.

Tedeschi’s lab discovered in mice that gabapentin helped recover upper limb function after a spinal cord damage in a 2019 research.

The fundamental goal of therapy after an ischemic stroke is to restore blood flow to the brain as soon as feasible, however this study reveals that gabapentin has no impact at that stage: The recovery rates were comparable whether the therapy began one hour or one day after the stroke.

The effects of the medicine, on the other hand, are seen in certain motor neurons, whose axons transport signals from the central nervous system to the body that direct muscles to move.

The researchers discovered that following a stroke in study mice, neurons on the unaffected, or contralateral, side of the brain began sprouting axons that restored signals for upper extremity voluntary movement that had been suppressed by cell death after the stroke. This is an example of plasticity, the capacity of the central nervous system to repair damaged structures, connections, and messages.

“The mammalian nervous system has some natural potential to self-repair,” Tedeschi, who is also a member of the Chronic Brain Injury Program at Ohio State, said. “However, we discovered that this increase in spontaneous flexibility was insufficient to induce recovery.” The functional losses in this experimental model of ischemic stroke are not as severe, but they remain.”

Following an injury, neurons have a propensity to become “hyperexcited,” resulting in increased signalling and muscular contractions that can cause uncontrollable movement and discomfort. While the neural receptor protein alpha2delta2 aids in the development of the central nervous system, its overexpression following neuronal trauma means it slows axon growth at inappropriate periods, contributing to this troublesome hyperexcitability.

Gabapentin works by blocking alpha2delta1/2 subunits and allowing post-stroke central nervous system healing to proceed in a coordinated manner.

“We inhibited the receptor with the medication and wondered if additional plasticity would occur.” Tedeschi said, “The answer is yes.”

Tedeschi believes the medicine normalises circumstances in the injured nervous system to encourage cortical remodelling in a functionally relevant way since a method that temporarily muted the new circuitry reversed behavioural signals of healing.

Mice who got six weeks of daily gabapentin therapy restored fine motor function in their forelimbs compared to control mice that did not get the medicine. Researchers discovered that functional benefits remained two weeks after therapy was discontinued.

“This indicated that functional alterations in the nervous system are consolidated,” Tedeschi stated.

Gabapentin also appeared to have an effect on non-neuron cells that regulate the timing of message transmission in the stroke-affected brain. An analysis of their activity following the drug treatment revealed that these cells may adjust their behaviour dynamically in response to changes in synaptic connectivity, allowing for smooth sprouting of axons that were compensating for the lost neurons.

The team is still researching the mechanics of stroke recovery, but Tedeschi believes the data indicate gabapentin offers potential as a therapy method for stroke repair.

The National Institute of Neurological Disorders and Stroke and the National Institutes of Health funded this research, as did the Chronic Brain Injury Discovery Theme at Ohio State.