Fig. 10.

The effect of hyperglycaemia on blood–brain barrier (BBB) integrity in the absence or presence of therapeutic hypothermia alone or together with inhibitors targeting PKC-β or Nox2. Through successive activation of diacylglycerol and PKC-β, hyperglycaemia increases the activity of NADPH oxidase which ultimately leads to BBB breakdown through generating excessive levels of superoxide anion, activating transcription factor NF-κB and regulating the synthesis, release and recruitment of various inflammatory mediators. Induction of stress fibre formation, tight junction reorganisation, apoptosis as well as inhibition of the proliferative and migratory capacity of endothelial cells and astrocytes also appear to contribute to the overall BBB damage. While treatments with therapeutic hypothermia alone effectively suppress the deleterious effects of hyperglycaemia on BBB, its combination with approaches negating the activity of PKC-β or Nox2 provide greater BBB-restorative capacity