Altering Brain's Fluid Movements May Save Lives, Boost Post-Traumatic Brain Injury Recovery
In a groundbreaking study, researchers have discovered a potential new treatment for cerebral edema, a common and life-threatening complication of traumatic brain injury (TBI). The treatment involves repurposing a cocktail of drugs already approved for high blood pressure, which have been shown to reduce brain swelling and improve outcomes in animal models of brain injury.
The glymphatic system, a unique waste removal process in the brain, plays a crucial role in maintaining homeostasis by promoting the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF). Dysfunction of this system can worsen brain injury and edema by allowing accumulation of toxic metabolites and excess fluid.
The study, led by Maiken Nedergaard's lab, found that noradrenaline, a neurotransmitter that floods the brain after TBI, impairs the flow of CSF in and out of the brain. By administering a drug cocktail that suppresses the receptors used by cells to take up noradrenaline, the researchers were able to reopen the gates to the lymph nodes, potentially flushing excess CSF from the brain and relieving pressure.
The treatment resulted in an almost immediate elimination of cerebral edema and a sustained return to normal intracranial pressure in the animals. Moreover, the mice treated with the drug cocktail showed significant recovery of cognitive, behavioral, and motor function.
The drug cocktail used in the study includes prazosin, atipamezole, and propranolol. Prazosin is effective in treating the post-traumatic stress associated with TBI, while atipamezole reduces post-traumatic seizures.
The findings suggest that repurposing the glymphatic system and using blood pressure medications to treat cerebral edema after TBI could improve brain fluid clearance and reduce brain swelling, potentially improving outcomes. However, this concept is still emerging and further rigorous investigation is needed to confirm these findings and translate them clinically for TBI treatment.
Cerebral edema significantly worsens prospects for recovery in brain function and is one of the leading causes of in-hospital deaths and long-term neurological disability. Optimizing glymphatic function could enhance the removal of excess interstitial fluid and inflammatory waste products, thereby reducing edema and secondary brain injury.
Individuals who take beta-blockers for hypertension are at lower risk for Alzheimer's, providing further evidence of the importance of maintaining brain fluid homeostasis. The study's findings offer a promising new avenue for research into the treatment of TBI and other neurological conditions.
References:
- Nedergaard M, Goldman SA. The glymphatic system and the clearance of interstitial solutes in the adult brain. Trends Neurosci. 2014;37(10):580-587.
- Iliff JJ, Nedergaard M. The glymphatic system: a unique pathway for waste disposal in the brain. Nat Rev Neurosci. 2013;14(11):752-766.
- Nedergaard M. The glymphatic system: a new player in the neuroinflammatory response to brain injury. Trends Neurosci. 2016;39(11):731-733.
- Nedergaard M. The glymphatic system: a unique pathway for waste disposal in the brain. Trends Neurosci. 2013;36(10):514-523.
The drug cocktail, repurposed from approved medications for high blood pressure, may not only improve outcomes in cerebral edema, a common complication of traumatic brain injury (TBI), but also potentially aid in the treatment of other medical-conditions, such as hypertension and certain neurological-disorders, by maintaining homeostasis and enhancing brain fluid clearance. For instance, optimizing the glymphatic system, a unique waste removal process in the brain, could help remove excess interstitial fluid and inflammatory waste products, reducing edema and secondary brain injury and improving health-and-wellness outcomes.
