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Early intervention following traumatic brain injury reduces epilepsy risk

UC Riverside-led rat study finds an immune receptor in the hippocampus is responsible for the onset of the disease after brain injuries

日期:
February 27, 2020
Source:
University of California - Riverside
Summary:
A research team has found that brains treated with certain drugs within a few days of an injury have a dramatically reduced risk of developing epilepsy later in life. The development of epilepsy is a major clinical complication after brain injury, and the disease can often take years to appear.
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A research team led by a scientist at the University of California, Riverside, has found that brains treated with certain drugs within a few days of an injury have a dramatically reduced risk of developing epilepsy later in life.

The development of epilepsy is a major clinical complication after brain injury, and the disease can often take years to appear.

“在老鼠的免疫反应系统国防部els that of humans, we identified that after brain injury a certain immune system receptor makes the brain more excitable, which promotes development of epilepsy," said Viji Santhakumar, an associate professor of molecular, cell, and systems biology at UC Riverside and the lead author of the study that appears in theAnnals of Neurology. "If this receptor can be suppressed, preferably within a day after injury, the future development of epilepsy can be reduced if not entirely prevented."

The receptor in question is the Toll-like receptor 4, or TLR4, an innate immune receptor. Following a brain injury, TLR4 increases excitability in the dentate gyrus of the hippocampus, the brain structure that plays a major role in learning and memory.

Santhakumar explained two factors are involved in brain injury: a neurological complication and the immune system. These factors have traditionally been studied separately, she said.

"Our team, however, studied these factors together," she added. "This approach helped us understand that the immune system operates through a very different mechanism in the injured brain than in the uninjured brain. Understanding the difference can guide us on how best to target treatments aimed at preventing epilepsy after traumatic brain injury."

The team specifically studied concussions, the kind suffered by many football players, which can lead to cell death in the hippocampus, affecting the processing of memory. Cell death activates the immune system, including TLR4. TLR4, in turn, increases excitability in the hippocampus.

"What our rat studies on traumatic brain injury show is that if we target early changes in excitability, we can alter long-term pathology," Santhakumar said. "Blocking TLR4 signaling shortly after brain injury reduces neuronal excitability in the hippocampus and seizure susceptibility. This seizure susceptibility is not reduced if we delay the blocking of TLR4 signaling after injury."

Paradoxically, Santhakumar's team found that drugs such as Resatorvid, which block TLR4 in the injured brain, caused epilepsy in uninjured brains.

"This paradox is difficult to understand," Santhakumar said. "We are currently looking at molecular signaling pathways in injured and uninjured brains to make sense of it."

The study could have important implications for war veterans returning home with brain injuries.

"Most often, the consequences of their injuries don't show up a year later, but several years later," said Santhakumar, who came to UCR in 2018 from Rutgers University.

The study focused only on epilepsy, one of several pathologies that can follow brain injury.

"Deficits in memory, cognition, and social behaviors could also follow brain injury," Santhakumar said. "In future work, we plan to study co-morbidities associated with traumatic brain injury."

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Story Source:

Materialsprovided byUniversity of California - Riverside. Original written by Iqbal Pittalwala.注意:内容可能被编辑风格d length.


Journal Reference:

  1. Akshata A. Korgaonkar, Ying Li, Dipika Sekhar, Deepak Subramanian, Jenieve Guevarra, Bogumila Swietek, Alexandra Pallottie, Sukwinder Singh, Kruthi Kella, Stella Elkabes, Vijayalakshmi Santhakumar.Toll‐like Receptor 4 Signaling in Neurons Enhances Calcium‐Permeable α‐Amino‐3‐Hydroxy‐5‐Methyl‐4‐Isoxazolepropionic Acid Receptor Currents and Drives Post‐Traumatic Epileptogenesis.Annals of Neurology, 2020; DOI:10.1002/ana.25698

Cite This Page:

University of California - Riverside. "Early intervention following traumatic brain injury reduces epilepsy risk: UC Riverside-led rat study finds an immune receptor in the hippocampus is responsible for the onset of the disease after brain injuries." ScienceDaily. ScienceDaily, 27 February 2020. .
University of California - Riverside. (2020, February 27). Early intervention following traumatic brain injury reduces epilepsy risk: UC Riverside-led rat study finds an immune receptor in the hippocampus is responsible for the onset of the disease after brain injuries.ScienceDaily. Retrieved June 29, 2023 from www.koonmotors.com/releases/2020/02/200227160546.htm
University of California - Riverside. "Early intervention following traumatic brain injury reduces epilepsy risk: UC Riverside-led rat study finds an immune receptor in the hippocampus is responsible for the onset of the disease after brain injuries." ScienceDaily. www.koonmotors.com/releases/2020/02/200227160546.htm (accessed June 29, 2023).

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