Deep Dive:
Post-traumatic epilepsy (PTE) is one of the most devasting consequences of a traumatic brain injury (TBI). Depending on the severity of the injury, anywhere from 5% to 53% of people with TBI may develop PTE [1,4,5], and, unfortunately, PTE is often resistant to currently available antiseizure medications. Importantly, there is often a span of time between the injury and the onset of epilepsy, known as the “latent period,” during which treatments could be initiated to either reduce the chance of or completely prevent PTE [1,6].
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One potential cause of PTE is inflammation in the brain. In hopes of preventing PTE or decreasing the probability of it developing, researchers are working to understand the role of inflammation in the brain as a means to prevent PTE. The inflammatory process is regulated by “parent” proteins that, when activated, bind to target receptors to subsequently activate downstream signaling pathways. One of these “parent” proteins is known as HMGB1, and two of its receptor partner systems are TLR4 and RAGE [7]. All three of these proteins have been implicated in development of seizures, a process called epileptogenesis [8,9]. With funding from CURE Epilepsy, Dr. Jin and his team at the Stark Neurosciences Institute of the Indiana University School of Medicine sought to determine if these proteins also played a role in PTE and whether inhibiting these pathways could represent an approach for reducing the likelihood of epileptogenesis and PTE following TBI [10].
To test their hypothesis, the researchers first confirmed that the expression of HMGB1, RAGE, and TLR4 increased in three types of brain cells (neurons [“regular” nerve cells], astrocytes, and microglia) in their PTE mouse model [3,10] soon after injury. After completing this initial experiment, the team evaluated the ability of inhibitors of TLR4 or RAGE to lower seizure susceptibility and frequency in their PTE mice.
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Your support makes this research possible. Our researchers’ important work continues through the current public health crisis and beyond thanks to generous donors who, like us, envision a world without epilepsy.
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Our mission is to find a cure for epilepsy, by promoting and funding patient-focused research. CURE Epilepsy is a non-profit 501(c)(3) tax-exempt organization. Our tax identification number is 36-4253176.
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