The University of Virginia research team found that the microglia healed the damaged cells, rather than consuming them, by forming a pouch around the damaged cells, coined “microglial process pouches” by the researchers. The pouches remained on the damaged and swollen nerve cells for hours, shrinking over time and leaving healed dendrites in their wake.
The development of antiepileptic drugs has largely centered on targeting known neural processes. With one-third of epileptic patients being resistant to existing medications, a figure that hasn’t altered in 30 years, it’s clear a new approach needs to be taken.
Epilepsy is a neurological disorder characterized by abnormal neuronal activity resulting in seizures, and can strike anyone at any time. Males and females regardless of race, ethnic background, and age can be affected by epilepsy.
In a recently published study, researchers at the University of Virginia School of Medicine outlined how they uncovered a new mechanism by which the brain repairs itself in response to severe seizures. The new discovery may help direct new development of pharmaceutical therapies by providing an alternative mechanism for drugs to target.
The team of researchers found that the microglia in the brain performed something never seen before. Not only did the immune cells remove brain debris after a seizure, the microglia actually stuck around to heal the neurons. The microglia didn’t consume the damaged cells, but healed them rather.
“We did not find microglia to be ‘eating’ the neuronal elements in this context. Rather, we saw a strong correlation between these interactions and a structural resolution of injured neurons suggestive of a ‘healing’ process,” said Dr. Ukpong B. Eyo of UVA’s Department of Neuroscience.
The microglia did this by creating a pouch around the damaged cells, which the team calls “microglial process pouches.” The pouches stayed on the damaged and swollen nerve cells for hours, growing smaller over time, and leaving behind healed dendrites. These long-lived pouches correlated with the structural resolution of dendrites.
The paper indicates that mice were given medication, specifically kainic acid, which induced both severe and mild seizures. Two photon microscopy, a fluorescence imaging technique used to examine tissues, was then used to examine the brains of these mice after the neurochemical-induced seizures.
The novel research that discovered the newly identified neuronal-healing process administered using “microglial process pouches” gives an entirely new role to microglia, a component of the nervous system previously thought to be well-known, and could serve a great deal in the advancement of epileptic medication.
“There has been mounting generic support for the idea that microglia could be used to ameliorate seizures, but direct, visualized evidence for how they could do this has been lacking,” Dr. Eyo added. “Our results indicate that microglia may not be simply clearing debris but providing structural support for neuronal integrity that may have implications even beyond the scope of seizures and epilepsy.”
The study was published in Cell Reports, on July 23rd, 2021.
Abstract. Although an imbalance between neuronal excitation and inhibition underlies seizures, clinical approaches that target these mechanisms are insufficient in containing seizures in patients with epilepsy, raising the need for alternative approaches. Brain-resident microglia contribute to the development and stability of neuronal structure and functional networks that are perturbed during seizures. However, the extent of microglial contributions in response to seizures in vivo remain to be elucidated. Using two-photon in vivo imaging to visualize microglial dynamics, we show that severe seizures induce formation of microglial process pouches that target but rarely engulf beaded neuronal dendrites. Microglial process pouches are stable for hours, although they often shrink in size. We further find that microglial process pouches are associated with a better structural resolution of beaded dendrites. These findings provide evidence for the structural resolution of injured dendrites by microglia as a form of neuroprotection.
Eyo, Ukpong B., et al. “Microglia Provide Structural Resolution to Injured Dendrites after Severe Seizures.” Cell Reports, vol. 35, no. 5, 2021, p. 109080., doi:10.1016/j.celrep.2021.109080.
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