Decreased Haemodynamic Response and Decoupling of Cortical Gamma Band Activity and Tissue Oxygen Perfusion after Striatal Interleukin-1 Injection.

Background: Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow; known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study we set out to investigate if increased cerebral levels of IL-1 have a negative effect on neurovascular coupling in the cortex in response to sensory stimulation. Methods: We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intrastriatal injection of interleukin-1β or vehicle. First, we used two dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of IL-1β. Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a ‘Clark-style’ electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs) respectively. Results: 2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1β injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1β injection, significant changes compared to vehicle being seen for gamma-band activity after 1 h and beta-bandactivity after 3 h. The amplitude of the functional pO2 response similarly decreased after 3 h post IL-1β injection, whereas IL-1β had no significant effect on the peak of whisker-stimulation-induced MUA. The stimulation-evoked increases in gamma power and pO2 correlated significantly throughout the 6 h in the vehicle group, but such a correlation was not observed in the IL-1β-injected group. Conclusions: We conclude that intrastriatal IL-1β decouples cortical neuronal activity from its haemodynamic response. This finding may have implications for neurological conditions where IL-1β plays a part, especially those involving reductions in cerebral blood flow (such as stroke).