Following traumatic brain injury (TBI) there is significant neuropathology which includes mitochondrial dysfunction, loss of cortical grey matter, microglial activation, and cognitive impairment. Previous evidence has shown that activation of the peroxisome proliferator-activated receptors (PPARs) provide neuroprotection following traumatic brain and spinal injuries. In the current study we hypothesized that treatment with the PPAR ligand Pioglitazone would promote neuroprotection following a rat controlled cortical impact model of TBI. Animals received a unilateral 1.5mm controlled cortical impact followed by administration of pioglitazone at 10mg/kg beginning 15 minutes after the injury and subsequently every 24hrs for five days. Beginning one day after the injury there was significant impairment in mitochondrial bioenergetic function which was attenuated by treatment with Pioglitazone at 15 minutes and 24 hours (p<0.05). In an

Con A-induced iNOS expression in the liver is dependent on the activation of NF-kappaB.

ATP-sensitive potassium channels (KATP) play a crucial role in coupling metabolic energy to the membrane potential of cells, thereby functioning as cellular "metabolic sensors." Recent evidence has showed a connection between the amyloid neurotoxic cascade and metabolic impairment. With regard to their neuroprotection in other neuronal preparations, KATP channels may mediate a potential neuroprotective role in Alzheimer's disease (AD). To investigate the effects of Abeta1-42 on the subunits of KATP expression in cultured primary rat basal forebrain cholinergic neurons, primary rat basal forebrain neurons were cultured and evaluated. The subunits of KATP: Kir6.1, Kir6.2, SUR1 and SUR2 expressing changes were observed by double immunofluorescence and immunoblotting when the neurons were exposed to Abeta1-42(2 microM) for different time (0, 24, 72 h). We found a significant increase in the expression of Kir6.1 and SUR2 in the cultured neurons being exposed to Abeta1-42 for 24 h, while Kir6.2 and SUR1 showed no significant change. However, after being treated with Abeta1-42 for 72 h, the expression of the four subunits was all increased significantly compared with the control. These findings suggest that being exposed to Abeta1-42 for different time (24 and 72 h) induces differential regulations of KATP subunits expression in cultured primary rat basal forebrain cholinergic neurons. The change in composition of KATP may contribute to resist the toxicity of Abeta1-42.

The ATP-sensitive potassium channel (KATP) play a crucial role in coupling metabolic energy to the cell membrane potential, β-amyloid peptide (Aβ) neurotoxicity has been associated with cellular oxidative stress and metabolic impairment. Whether there is an interaction between KATP and Aβ or not? The expression of KATP subunits was to be investigated after the cultured primary rat basal forebrain cholinergic neurons being exposed to Aβ₁₋₄₂. The subunits of KATP: Kir6.1, Kir6.2, SUR1 and SUR2 expressing change was observed by double Immunofluorescence and immunoblotting in cultured cholinergic neurons from different groups: treatment with Aβ₁₋₄₂ (group Aβ₁₋₄₂), pretreatment with diazoxide and then exposure to Aβ₁₋₄₂ (group diazoxide + Aβ₁₋₄₂), and the control (group control). The results showed that in response to the treatment with Aβ₁₋₄₂ (2 μmol/L) for 24 h, the expression of Kir6.1 and SUR2 were significantly up-regulated, while this change can be partly reversed by pretreatment with diazoxide (1 mmol/L) for 1 h. There were significant increases in all KATP subunits expression levels after exposure to Aβ₁₋₄₂ for 72 h. However, the up-regulation of Kir6.1, Kir6.2 and SUR2 except SUR1 can be partly reversed by pretreatment with diazoxide (1 mmol/L) for 1 h. It is concluded that exposure to Aβ₁₋₄₂ for different time (24 and 72 h) induced differential regulation of KATP subunits expression in cultured primary rat basal forebrain cholinergic neurons. The change in composition of KATP may contribute to the dysfunction of KATP and membrane excitability disturbance. The effect of diazoxide on KATP subunits expression may explain, in part, the resistance of diazoxide to the toxicity of Aβ₁₋₄₂.