Altering Cerebral Fluid Streams May Reduce Death Rates, Enhance Recovery After Brain Trauma Injuries
In a groundbreaking study, researchers have proposed using blood pressure medications to treat cerebral edema, a common consequence of traumatic brain injury (TBI) that significantly increases the risk of death and worsens prospects for recovery in brain function.
The study, supported by several prestigious research foundations, focused on the glymphatic system, a unique waste removal process in the brain first described by Maiken Nedergaard's lab in 2012. Noradrenaline, a neurotransmitter that floods the brain immediately after TBI, is a main trigger of cerebral edema. The study found that noradrenaline interferes with the function of the glymphatic system, specifically restricting the movement of cerebrospinal fluid (CSF) through the section of the system's plumbing where CSF drains from the brain and flows into the meningeal and cervical lymph nodes in the neck.
To combat this, the team used a cocktail of drugs, including prazosin, atipamezole, and propranolol, to suppress noradrenaline and restart the glymphatic system's fluid flow. The treatment resulted in significant recovery of cognitive, behavioral, and motor function in the mice.
Prazosin, another drug used, is effective in treating the post-traumatic stress associated with TBI. Atipamezole, one of the drugs used, reduces post-traumatic seizures. Beta-blockers, another component of the drug cocktail, have been observed to reduce in-hospital mortality and improve functional outcome of TBI patients.
The new research suggests repurposing the glymphatic system to act as an emergency pressure release valve by reopening the gates to the lymph nodes to flush excess CSF from the brain, thereby relieving pressure. The treatment, when administered to mice soon after TBI, led to an almost immediate elimination of cerebral edema and a sustained return to normal intracranial pressure.
However, it's important to note that currently, there is no established evidence or clinical practice supporting the use of blood pressure medications specifically to treat cerebral edema in TBI by targeting the glymphatic system. Standard treatments for cerebral edema include hyperosmolar therapy such as mannitol or hypertonic saline to reduce brain swelling and intracranial pressure, and systemic glucocorticoids like dexamethasone for vasogenic edema to reduce inflammation.
The drugs used in the study have observed neurological benefits and have the potential to move quickly to clinical studies to confirm these findings. The researchers hope that this approach could lead to a new and effective treatment for TBI, a condition that affects millions of people worldwide each year.
The study was conducted by a team of researchers from several universities, including the University of Rochester, the University of Copenhagen, the Universities of Rochester and Copenhagen, the University of Minnesota, Tulane University, and the University of Missouri. The research was supported by funding from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the National Institute of Neurological Disorders and Stroke, the Burroughs Wellcome Fund, the Joint Programme-Neurodegenerative Disease Research, the Novo Nordisk Foundation, the Lundbeck Foundation, and the US Army Research Office.
Individuals who take beta-blockers for hypertension are at lower risk for Alzheimer's, according to research by Nedergaard and her colleagues at the University of Copenhagen. The glymphatic system's mechanics have been better understood due to advanced imaging technologies and AI-driven models of fluid dynamics. As research into the glymphatic system’s role in TBI continues, it may yield established therapeutic approaches involving antihypertensive drugs.
- This groundbreaking study suggests a potential role for antihypertensive drugs, such as those used to treat medical-conditions like high blood pressure, in the treatment of neurological-disorders, specifically traumatic brain injury (TBI), by targeting the glymphatic system's function and reducing cerebral edema.
- Further research into the glymphatic system, a unique waste removal process in the brain, may reveal other medical-conditions, including Alzheimer's, that can be managed or treated using health-and-wellness strategies involving antihypertensive drugs, such as those commonly used for hypertension.
