Altering Cerebral Liquid Movements Potentially Saves Lives, Enhances Post-Traumatic Brain Injury Recuperation
A new study published in Nature suggests that some drugs already approved to treat high blood pressure could potentially be repurposed to treat cerebral edema, a common consequence of traumatic brain injury (TBI).
The study, supported by funding from several organizations including the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the National Institute of Neurological Disorders and Stroke, and the US Army Research Office, found that antihypertensive drugs such as calcium channel blockers, beta blockers, and certain diuretics could help reduce cerebral edema.
These drugs work primarily by modulating blood vessel tone and permeability, which can reduce fluid leakage into brain tissue and consequently decrease edema. Calcium channel blockers stabilize blood vessel walls, preventing excessive fluid from leaking into the brain parenchyma. Beta blockers lower blood pressure, decreasing the hydrostatic pressure in cerebral capillaries, while some diuretics promote fluid excretion, reducing vascular pressure driving edema.
The treatment resulted in an almost immediate elimination of cerebral edema and a sustained return to normal intracranial pressure in the animals. Moreover, it led to significant recovery of cognitive, behavioral, and motor function in the animals.
The researchers achieved these results by administering a cocktail of drugs to mice soon after TBI. The cocktail included prazosin, atipamezole, and propranolol, drugs that collectively suppress the receptors used by cells to take up noradrenaline, a neurotransmitter that impairs the flow of cerebrospinal fluid (CSF) in and out of the brain after TBI.
The researchers propose that reopening the gates to the lymph nodes could flush excess CSF from the brain, thereby relieving pressure. Using fluorescent microspheres, they traced CSF originating from the site of the swelling as it exited in bulk from the brain via the lymphatic vessels.
The researchers speculate that these drugs could be moved quickly to clinical studies to confirm these findings. If successful, these drugs could offer a more accessible treatment option compared to experimental drugs currently under investigation.
Current standard treatments for cerebral edema include osmotic agents like mannitol and corticosteroids, which reduce swelling by drawing water out of brain tissue or reducing inflammation, respectively. In contrast, the antihypertensive drugs address the vascular component of edema formation by controlling blood pressure and vascular permeability, thereby complementing current therapies.
The glymphatic system, a unique waste removal process in the brain, was first described by Maiken Nedergaard's lab in 2012. The researchers believe that the glymphatic system has potential to treat Alzheimer's and other neurological disorders, and more effectively deliver and distribute drugs in the central and peripheral nervous system, including the inner ear.
Nedergaard and her colleagues at the University of Copenhagen have shown that individuals who take beta-blockers for hypertension are at lower risk for Alzheimer's. The study adds to the growing body of evidence suggesting that the glymphatic system and its related mechanisms play a crucial role in brain health.
Cerebral edema is one of the leading causes of in-hospital deaths and is associated with long-term neurological disability. The findings of this study could pave the way for new treatments for TBI and other conditions associated with brain swelling.
- These antihypertensive drugs, such as calcium channel blockers, beta blockers, and certain diuretics, which were found to help reduce cerebral edema in TBI cases, could potentially be used to treat other medical-conditions involving neurological-disorders and health-and-wellness issues related to brain swelling.
- The glymphatic system, a unique waste removal process in the brain, has the potential to treat not only traumatic brain injury and cerebral edema but also other neurological-disorders, such as Alzheimer's, and potentially improve drug distribution in the central and peripheral nervous system, including the inner ear.
