Scientists have achieved a breakthrough in reinstating lost brain function in mouse models of stroke by utilizing small molecules. These molecules hold the potential for future development into a therapeutic approach for stroke recovery. Tadeusz Wieloch, senior professor of neurobiology at Lund University in Sweden, explains, “Communication between nerve cells in extensive brain regions undergoes changes after a stroke, and we demonstrate that this can be partially restored with the treatment.”
Remarkably, the treatment initiated several days after a stroke proved effective in restoring lost somatosensory functions in rodents, a condition experienced by approximately 60% of stroke patients. In ischemic strokes, where inadequate blood flow to the brain causes damage, resulting in nerve cell loss, this groundbreaking treatment offers hope for mitigating effects such as paralysis, sensorimotor impairment, vision and speech difficulties, as well as pain and depression.
Currently, there are no approved drugs, aside from clot-dissolving treatment within the first 4.5 hours of a stroke, that enhance or restore functions post-stroke. Spontaneous improvements occur, but many patients suffer chronic functional losses. The recent international study, led by Lund University in collaboration with the University of Rome La Sapienza and Washington University at St. Louis, presents promising outcomes in mice and rats treated with substances inhibiting the metabotropic glutamate receptor (mGluR5) – a key regulator of communication in the brain’s nerve cell network.
Wieloch notes, “Rodents treated with the mGluR5 inhibitor regained their somatosensory functions.” Even when the treatment commenced 10 days after a stroke, some function improvement was observed. The study revealed that while the extent of brain damage remained unchanged, sensorimotor functions improved. This is attributed to the connectome, the intricate network of nerve cells in the brain, and how the mGluR5 receptor plays a crucial role in its reduced activity, which the inhibitor counteracts to restore lost brain function.
Moreover, combining the mGluR5 inhibitor treatment with somatosensory training, involving enriched environments for rodents, further enhanced sensorimotor function. The researchers envision that their findings could pave the way for clinical treatments initiated shortly after an ischemic stroke, potentially offering a promising approach when combined with rehabilitation training. However, further studies are necessary, as the current research involved mice and rats and must be replicated in human trials. Tadeusz Wieloch emphasizes the need for additional investigations, stating, “This should be possible since several mGluR5 inhibitors have been studied in humans for the treatment of neurological diseases other than stroke and shown to be tolerated by humans.” The research received support from the Swedish Research Council, Alborada Trust, Hans-Gabriel and Alice Wachtmeister Foundation, and the Multipark Strategic Research Area.
