Effect of Difluoromethylornithine Treatment on Regional Ornithine Decarboxylase Activity and Edema Formation after Experimental Brain Injury

Abstract

This study examined the effect of difluoromethylornithine (DFMO) on regional activities of ornithine decarboxylase (ODC) and edema formation in bilateral cerebral cortex and hippocampus after a unilateral controlled cortical-impact (CCI) injury in rats. To measure the activity of ODC, the brains of injured and control rats were frozen in situ at 30 min, 3, 6, and 24 h after CCI brain injury of moderate severity. The specific gravity, an indicator of edema formation, was examined in decapitated animals at corresponding time points. Brain injury induced significant increases of ODC in the ipsilateral hippocampus, adjacent and injury-site cortices, and in the contralateral cortex and hippocampus at 3 and 6 h after injury. No significant edema formation was found in any brain region at 30 min after injury. A significant edema formation was first found only in the injury-site cortex at 3 h after injury. At 6 and 24 h after injury, significant edema was found in all regions ipsilateral to the injury-site. At 24 h after injury, significant but less severe edema was also found in the contralateral cortex and hippocampus. DFMO, an irreversible inhibitor of ODC, abolished the increase in ODC in all regions. It also attenuated edema formation in the adjacent cortex and in the contralateral cortex and hippocampus. These findings indicate that polyamines may play a role in posttraumatic brain edema formation, particularly in important brain regions remote from the injury-site.

Role of spermine in amyloid ?-peptide-associated free radical-induced neurotoxicity

“…A␤ is shown to oxidize numerous neuronal proteins (Aksenov et al, 1997;Butterfield, 1997;Yatin et al, 1998Yatin et al, , 1999bButterfield et al, 1999). In previous studies polyamine biosynthesis inhibitors were reported as neuroprotective agents (Kindy et al, 1994;Baskaya et al, 1996). These agents may protect the neurons from overaccumulation of polyamines to toxic levels by inhibiting the specific enzymatic pathways.…”

Activation of Ornithine Decarboxylase and Accumulation of Putrescine after Traumatic Brain Injury

“…Regional changes in ODC activity correlated with edema formation after traumatic brain injury. In another study DFMO treatment decreased omithine decarboxylase activity and edema formation after experimental brain injury (Baskaya et al, 1996b). However, changes in putrescine or polyamines were not measured after injury.…”

Delayed Administration of Alpha-Difluoromethylornithine Prevents Hippocampus-Dependent Cognitive Impairment after Single and Combined Injury in Mice

“…Difluoromethylornithine (DFMO) was synthesized almost 30 years ago as an irreversible inhibitor of ornithine decarboxylase (ODC). It was shown that DFMO decreased edema after cortical impact (5) and ischemic injury volume after experimental cerebral ischemia (3). Our earlier work showed that DFMO treatment reduced radiation-induced necrosis, vascular permeability and associated vasogenic edema after focal radiation-induced injury (6–8).…”