WHOM THE HELL do we go to to get this tested for stroke survivors? It sounds promising for memory problems. I want a specific name to have responsibility to drive this thru to completion. That is just basic Management 101, which obviously the stroke medical world is oblivious to. But they are at Ph.D levels in incompetence.
2 years ago this came out. Did your fucking failure of a hospital do ONE DAMN THING WITH IT?
It was in rats so your doctor and stroke hospital were responsible to followup with researchers to get this tested in humans. Failure to do so should be grounds for firing. I hate keeping incompetent people in their jobs.
Ursolic Acid Ameliorates Inflammation in Cerebral Ischemia and Reperfusion Injury Possibly via High Mobility Group Box 1/Toll-Like Receptor 4/NFκB Pathway May 2018
How memory function could be preserved after brain injury
A study examining the effect of the immune
receptor known as Toll-like Receptor 4, or , on how memory functions
in both the normal and injured brain has found vastly different
cellular pathways contribute to the receptor's effects on excitability
in the uninjured and injured brain.
Further, the researchers found novel mechanisms for how TLR4 regulates memory function in the normal, uninjured brain.
The study, performed on rats and published in Brain, Behavior, and Immunity, has the potential to lead to treatments aimed at limiting memory deficits after brain injury.
"Memory deficits are a major long term adverse consequence of brain injury and the ability of a drug treatment given a day after injury to improve memory function is of significant clinical interest," said Viji Santhakumar, an associate professor of molecular, cell and systems biology at the University of California, Riverside, who led the study. "Resatorvid, a drug approved for clinical trials in other diseases, effectively blocked TLR4 and improved post-injury memory deficits in our study."
"We found suppressing TLR4 signaling a day after concussive brain injury, common to sports and traffic accidents, reduces excitability and improves working memory performance a week to a month later," she said. "Our data show the processes underlying the damaging effects of brain injury can be selectively manipulated for therapy and can preserve memory function after the injury."
How exactly TLR4 affects memory function in the normal and injured brain is not clear.
"While the actual mechanisms are not known, the speculation is that TLR4 regulates memory function by suppressing neuronal activity in the normal brain, thereby improving signal-to-noise ratio," Santhakumar said. "After injury, the effect of TLR4 flips to enhancing neuronal activity and promoting excitability, which increases noisy and non-specific neuronal firing and degrades signal-to-noise. It is possible that after injury TLR4 impairs cellular processes involved in memory formation, which my lab is currently investigating. The bottom line is that inhibiting TLR4 signaling in the injured brain leads to improvements in long-term working memory deficits for weeks to a month."
Next, Santhakumar and her team plan to determine how TLR4 signaling through glial mediators suppresses network excitability and facilitates memory performance in the normal brain. The researchers also plan to explore how neuronal TLR4 signaling after injury can be selectively manipulated.
"We are interested in determining if blocking TLR4 signaling after injury prevents network reorganization and abnormal changes in rhythmic or oscillatory brain activity that is crucial to memory processing," she said.
Santhakumar was joined in the study by Akshata A. Korgaonkar, the first author of the research paper who is a postdoctoral researcher at the Washington University School of Medicine in St. Louis; Susan Nguyen, Dipikar Sekhar, and Deepak Subramanian of UCR; and Ying Li, Jenieve Guevarra, and Kevin C. H. Pang of the Rutgers New Jersey Medical School, where Santhakumar, an expert in epilepsy and traumatic brain injury, worked before she joined the UCR faculty in 2018.
The study, performed on rats and published in Brain, Behavior, and Immunity, has the potential to lead to treatments aimed at limiting memory deficits after brain injury.
"Memory deficits are a major long term adverse consequence of brain injury and the ability of a drug treatment given a day after injury to improve memory function is of significant clinical interest," said Viji Santhakumar, an associate professor of molecular, cell and systems biology at the University of California, Riverside, who led the study. "Resatorvid, a drug approved for clinical trials in other diseases, effectively blocked TLR4 and improved post-injury memory deficits in our study."
The brain has neurons and non-neuronal cells called
glia. In the normal brain, the activity of neurons is suppressed by
TLR4; in the injured brain, TLR4 increases neuronal activity.
Specifically, following brain injury, TLR4 increases excitability in the
dentate gyrus, a circuit involved in memory processing in the
hippocampus, the brain structure that plays a major role in learning and
memory.
The UC Riverside-led study found only neurons are involved in
TLR4-mediated increase in excitability in the injured brain. In
contrast, glial cells are necessary for TLR4-mediated reduction of
excitability in the normal brain."We found suppressing TLR4 signaling a day after concussive brain injury, common to sports and traffic accidents, reduces excitability and improves working memory performance a week to a month later," she said. "Our data show the processes underlying the damaging effects of brain injury can be selectively manipulated for therapy and can preserve memory function after the injury."
How exactly TLR4 affects memory function in the normal and injured brain is not clear.
"While the actual mechanisms are not known, the speculation is that TLR4 regulates memory function by suppressing neuronal activity in the normal brain, thereby improving signal-to-noise ratio," Santhakumar said. "After injury, the effect of TLR4 flips to enhancing neuronal activity and promoting excitability, which increases noisy and non-specific neuronal firing and degrades signal-to-noise. It is possible that after injury TLR4 impairs cellular processes involved in memory formation, which my lab is currently investigating. The bottom line is that inhibiting TLR4 signaling in the injured brain leads to improvements in long-term working memory deficits for weeks to a month."
Santhakumar was intrigued by a common immune
signaling molecule, TNFα, which contributes to both TLR4-dependent
reduction in excitability in normal, uninjured brains, and TLR4-mediated
increase in excitability after concussive brain injury. In the normal
brain, glial cells are involved; in the injured brain, neurons are
involved.
"Our study has identified a novel role for neuronal TNFα in
regulating excitability," she said. "We were surprised that glial versus
neuronal signaling mediated by the same signaling molecule, TNFα, has
different effect on neuronal excitability."Next, Santhakumar and her team plan to determine how TLR4 signaling through glial mediators suppresses network excitability and facilitates memory performance in the normal brain. The researchers also plan to explore how neuronal TLR4 signaling after injury can be selectively manipulated.
"We are interested in determining if blocking TLR4 signaling after injury prevents network reorganization and abnormal changes in rhythmic or oscillatory brain activity that is crucial to memory processing," she said.
Santhakumar was joined in the study by Akshata A. Korgaonkar, the first author of the research paper who is a postdoctoral researcher at the Washington University School of Medicine in St. Louis; Susan Nguyen, Dipikar Sekhar, and Deepak Subramanian of UCR; and Ying Li, Jenieve Guevarra, and Kevin C. H. Pang of the Rutgers New Jersey Medical School, where Santhakumar, an expert in epilepsy and traumatic brain injury, worked before she joined the UCR faculty in 2018.
The study was supported by the National Institutes
of Health; Citizens United for Research in Epilepsy; and the state of
New Jersey.
Story Source:
Materials provided by University of California - Riverside. Original written by Iqbal Pittalwala. Note: Content may be edited for style and length.
Materials provided by University of California - Riverside. Original written by Iqbal Pittalwala. Note: Content may be edited for style and length.
Journal Reference:
- Akshata A. Korgaonkar, Susan Nguyen, Ying Li, Dipika Sekhar, Deepak Subramanian, Jenieve Guevarra, Kevin C.H. Pang, Vijayalakshmi Santhakumar. Distinct cellular mediators drive the Janus faces of toll-like receptor 4 regulation of network excitability which impacts working memory performance after brain injury. Brain, Behavior, and Immunity, 2020; DOI: 10.1016/j.bbi.2020.03.035
No comments:
Post a Comment