Scientists from the Cleveland Clinic report that a type of immune cell believed to exacerbate chronic adult brain diseases, such as Alzheimer’s and multiple sclerosis (MS), can actually protect the brain from traumatic brain injury (TBI) and may slow the progression of neurodegenerative diseases.
Their study (“Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain”) is published in Nature Communications.
The research team, led by Bruce Trapp, Ph.D., chair of the department of neurosciences at Cleveland Clinic's Lerner Research Institute, found that microglia can help synchronize brain firing, which protects the brain from TBI and may help alleviate chronic neurological diseases. They provided the most detailed study and visual evidence of the mechanisms involved in that protection.
"Our findings suggest the innate immune system helps protect the brain after injury or during chronic disease, and this role should be further studied," explained Dr. Trapp said. “The methods we developed will help us further understand mechanisms of neuroprotection."
Microglias are primary responders to the brain after injury or during illness. While researchers have long believed that activated microglia cause harmful inflammation that destroys healthy brain cells, some speculate a more protective role. Dr. Trapp's team used an advanced technique called 3D electron microscopy to visualize the activation of microglia and subsequent events in a mouse model.
They found that when chemically activated, microglia migrate to inhibitory synapses, connections between brain cells that slow the firing of impulses. They dislodge the synapse (called "synaptic stripping"), thereby increasing neuronal firing and leading to a cascade of events that enhance survival of brain cells.
“Electrophysiological recordings further establish that the reduction in inhibitory GABAergic synapses increased synchronized firing of cortical neurons in γ-frequency band,” wrote the investigators. “Increased neuronal activity results in the calcium-mediated activation of CaM kinase IV, phosphorylation of CREB, increased expression of antiapoptotic and neurotrophic molecules and reduced apoptosis of cortical neurons following injury. These results indicate that activated microglia can protect the adult brain by migrating to inhibitory synapses and displacing them from cortical neurons.”
"We could potentially harness the protective role of microglia to improve prognosis for patients with TBI and delay the progression of Alzheimer's disease, MS, and stroke,” said Dr. Trapp.