Brain mitochondrial swelling induced by arachidonic acid and other long chain free fatty acids

Polyunsaturated fatty acids (PUFAs), arachidonic acid in particular, are well known, potent inducers of edema in the brain, while monounsaturated and saturated long chain fatty acids do not possess this quality. This investigation has compared the ability of some free fatty acids (FFAs), known to be released during cerebral ischemia, to induce brain mitochondrial swelling in vitro. The PUFAs tested, especially arachidonic acid (20:4), were more potent in causing swelling than saturated or monounsaturated ones, as measured by the decrease in light absorbance of the mitochondrial suspension. This finding is in line with the unique potency of 20:4 to induce brain edema. Incubation of brain mitochondria with 20:4 for 20 min caused a dose-dependent swelling. ATP-MgCl2 both prevented and reversed this swelling, while binding of the 20:4 by the addition of bovine serum albumin could only prevent but not reverse the swelling. The contraction of the swollen mitochondria appeared to be mediated by a mechanism dependent upon high-energy phosphates, potentiated by MgCl2. The concentration of 20:4 required to induce swelling was about 20 times higher than the concentration required to induce inhibition of mitochondrial respiratory function (L Hillered and P H Chan: J Neurosci Res 19:94-100, 1988a). Moreover, reversal of the swelling occurred without recovery of respiratory function. These results suggest that swelling is a phenomenon of minor importance as an indicator of brain mitochondrial dysfunction, at least when induced by 20:4 in vitro.