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article imageTraumatic brain injury promised pharmaceutical treatment

By Karen Hardison     Dec 8, 2016 in Science
Fayetteville - Brain cell swelling follows and worsens traumatic brain injury. Scientists at the University of Arkansas found the drug Acetazolamide inhibits production of the protein triggering brain cell swelling, suggesting a treatment for brain injury.
Scientists found that the devastating effects of mild traumatic brain injury are mitigated, or lessened, by controlling brain cell swelling. A study at the University of Arkansas made a connection between an antiepeletic drug and reduction of cellular swelling, which follows brain injury and is closely tied to disability and death, following mild traumatic brain injury (mTBI).
Closed-skull, non-penetrating mTBIs are devastating brain injuries that can lead to serious conditions, including personality change, language loss, disability and even death. Biomedical engineering researchers Kartik Balachandran and Nasya Sturdivant found that the protein triggering brain swelling is inhibited when the antiepeletic, anti-edemic (anti-swelling) drug Acetazolamide (AZA) is administered following a simulated impact brain injury. The results of the study suggest a therapeutic treatment for devastating mild traumatic brain injuries.
Swelling in Brain Cells
Using a unique and originally designed benchtop bioreactor that allows for close examination of the brain's astrocyte cells — which comprise up to 50 percent of all brain cells at a 10 to one ratio — Balachandran and Sturdivant found in their study of AZA that swelling of astrocyte cells was reduced when AZA was present: "[There] was shown to be an acute increase in intracellular volume following mTBI, which was significantly reduced in the presence of AZA," as stated in the report published in Nature’s Scientific Reports.
Brain Fluid and Brain Injury
Previous studies showed a connection between brain injury and increased expression, or production, of the water channel protein aquaporin-4 (AQP4) in astrocyte cells. This increased expression causes a "massive cellular influx" of fluid causing an increase in astrocyte cell volume and in "cellular mortality." This connection suggested that antagonist regulation of post-injury expression of AQP4 protein might provide a therapeutic treatment for mTBIs. The anti-swelling diuretic AZA is known to be effective at inhibiting a similar water channel protein, AQP426. Balachandran and Sturdivant's study sought to examine the effect of AZA on the fluid triggering protein AQP4 following simulated injury to astrocyte cells. Kartik Balachandran, assistant professor of biomedical engineering, explained the role of AQP4:
Our study found that mild traumatic brain injury resulted in increased expression of a protein called aquaporin-4, which caused a massive cellular influx of fluid, leading to increased astrocyte cell volume and injury.
Simulated Cellular Impact
In the study, Balachandran and Sturdivant exposed sample astrocyte cells to simulated impact ("stretch"). They found that "there was a significant increase in cell swelling within 30 min of mTBI," with a "significantly increased" expression of aquaporin-4 protein measurable "24 hours after mTBI." AZA added to the astrocyte cells shortly before the "stretch" significantly reduced cell swelling and cell death. The study "data point to" astrocyte brain cell "swelling immediately following mTBI, and [to] AZA as a promising treatment to mitigate cellular mortality," with its consequent death or disabling injury.
mTBI Treatment and Warzones
This study places AZA as a therapeutic treatment for mTBIs, and, since researchers administered AZA before the simulated impact, AZA may potentially be explored as a mTBI preventative. Balachandran and Sturdivant addressed this study because of the prevalence of military personnel returning from war with non-penetrating mTBIs as a consequence of explosions in warzones. Attention has been turned to finding therapeutic treatment for these wartime injuries, as stated in the report:
An estimated 1.7 million TBIs occur annually in the United States with [only] approximately 70 percent treated in emergency hospitals. ... [T]he prominent role of improvised explosive devices in the Iraq and Afghanistan wars have led to an increase in the occurrence of TBIs and subsequently an escalation of clinical interest into blast-related TBI.
Causes of TBIs
Mild traumatic brain injuries are often caused by traffic accidents, sporting collisions and wartime explosions. Mitigating the consequences of mTBIs, often left undetected, is of great importance and is dramatically needful for returning veterans as well for children and teens engaged in sports. Non-penetrating TBIs are ranked from mild (previously called "concussion") to moderate to severe. Each level is associated with specific kinds of responsiveness in consciousness, motor function, verbal function and visual function, as measured on the Glasgow Coma Scale.
CDC Campaign Against TBIs
The Center for Disease Prevention and Control (CDC) is dedicated to raising public awareness of mTBIs and to improving medical detection and treatment of mTBIs since many go undetected (approximately 510,000 a year go undetected, approximately 30 percent of the 1.7 million that occur). CDC's initial effort was Heads Up focusing on children and teens injured in sporting events. The compass of CDC's efforts has expanded to include TBIs suffered by military personnel in warzones. The work done by Marine Lt. Col. Tim Maxwell to found the SemperMax Support Fund, dedicated to preventing wounded soldiers from feeling alienated and alone during recovery from TBIs, is highlighted in CDC efforts relating to warzone TBIs.
Balachandran and Sturdivant's findings were published in the September 2016 issue of [i]Nature’s Scientific Reports[/i].
More about University of arkansas, traumatic brain injury, astrocyte cells, aquaporin4 protein, acetazolamide
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