CYP4Fs expression in rat brain correlates with changes in LTB4 levels after traumatic brain injury

Cytochrome P450 (CYP) 4Fs constitute a subgroup of the cytochrome P450 superfamily and are involved in cellular protection and metabolism of numerous molecules, including drugs, toxins, and eicosanoids. CYP4Fs are widely distributed in rat brain with each isoform having a unique distribution pattern throughout different brain regions. The present study shows that traumatic brain injury (TBI) triggers inflammation and elicits changes in mRNA expression of CYP4Fs in the frontal and occipital lobes and the hippocampus. At 24 h post-injury, almost all CYP4F mRNA expression is suppressed compared with sham control throughout these three regions, while at 2 weeks post-injury, all CYP4F mRNAs increase, reaching levels higher than those at 24 h post-injury or uninjured controls. These changes in CYP4F levels inversely correlate with levels of leukotriene B4 (LTB4) levels in the brain following injury at the same time points. TBI also causes changes in CYP4F protein expression and localization around the injury site. CYP4F1 and CYP4F6 immunoreactivity increases in surrounding astrocytes, while CYP4F4 immunoreactivity shifts from endothelia of cerebral vessels to astrocytes.