Chondroitinase ABC Reduces Brain Tissue Swelling In Vitro

Increased intracranial pressure (ICP) caused by edema following severe traumatic brain injury (TBI) or stroke contributes to high rates of mortality and morbidity. The search continues for more effective treatments that target the edema that contributes to increased ICP. We previously described the effect of the fixed charge density (FCD) of brain on its swelling behavior according to the Donnan effect. Here we show that reduction of brain tissue FCD is an effective means of reducing brain tissue swelling and edema in rat and porcine cortical brain tissue in vitro. The effect of enzymes directed at digesting candidate contributors to cellular FCD such as chondroitin sulfate proteoglycans (CSPGs), heparin sulfate proteoglycans (HSPGs), and DNA was examined in slices of the adult rat cortex. All enzymes were capable of decreasing FCD in the tissue by similar to 20%, and reducing tissue swelling over a 24 h period following dissection from similar to 60% to similar to 30%. Chondroitinase ABC (ChABC) was most effective at reducing dead brain tissue swelling in response to changes in ionic osmotic environments. ChABC reduced swelling in live slices of tissue even within the first 2 h following dissection. It also significantly reduced the FCD, initial tissue swelling, and volume change in response to hypotonic bathing solution in porcine cortical brain tissue. The use of ChABC to reduce tissue FCD may be an effective method for reducing brain edema and controlling ICP following injury.