Confocal microscopy makes important discovery about seizure-related brain damage in epilepsy

Confocal microscopy has found the cause responsible for as much as half of seizure-related neuronal degeneration cases in epilepsy.

Researchers at the State University of New York (SUNY) Downstate Medical Center (Brooklyn, NY) have found that hypoxia (lack of oxygen) because of abnormal blood flow is responsible for as much as half of seizure-related neuronal degeneration cases in epilepsy. It was previously thought to be primarily caused by excitotoxicity, or over-stimulation of the neurons.

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A confocal microscopy technique enabled the research team to detect a cascade of abnormal capillary vasodynamics, which indicate that even though blood can be observed flowing into the hippocampus—a part of the brain that suffers damage from seizures—an unusually high number of microscopic vascular spasms block flow to some of the delicate brain tissue. This cumulative damage over a lifetime of seizures could contribute to severe cognitive decline or even death in patients with epilepsy. The study also discovered that microscopic spasms in capillaries occur, albeit with lower frequency, during normal brain function, too, suggesting that one problem caused by epilepsy is that seizures drive these vasospasms to abnormal levels.

The study delved further into the mechanism of the vasospasms and found that tiny cells on capillaries, called mural cells, are precisely associated with the points of the vasospasms in the vessels. This contributes to growing published literature suggesting that capillaries are not simply passive tubes through which blood cells flow to irrigate tissue, but rather they may actively contribute to the control of local blood flow directly.

In their study, the researchers examined the brain function of animals with epilepsy to distinguish between neuronal death caused by excitotoxicity vs. hypoxia. Helped by the recent development of fiber-optic-bundle-coupled laser-scanning confocal fluorescence imaging (confocal laser endomicroscopy), which allowed them to image blood flow more deeply in the brain, they were able to look more closely at the microvascular dynamics around the hippocampus, which is thought to be a critical region of seizure genesis in patients.

The research team was able to conclude that hypoxia was the cause for approximately half the neuronal death through a novel stereological analysis, which was able to identify neuronal death happening in close proximity to hypoxic blood vessels. Since excitotoxic neuronal death is not related to blood flow, the authors concluded that the nearby hypoxia may be to blame. Their hypothesis was borne out by a comparison to similar neuronal death in epileptic animals vs. healthy ones.

The researchers believe their findings suggest a potential value in treatment of epilepsy with blood flow regulating drugs to reduce the amount of seizure-related neurodegeneration.

Full details of the work appear in the journal Scientific Reports; for more information, please visit http://dx.doi.org/10.1038/srep43276.

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