Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection

Abstract

BackgroundNeurovascular 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 the neurovascular coupling in the cortex in response to sensory stimulation.MethodsWe 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 intra-striatal 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 interleukin-1β (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 (partial pressure oxygen, pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs), respectively.Results2D-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-band activity 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.ConclusionsWe conclude that intra-striatal 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).

Longitudinal study of hemodynamics and dendritic membrane potential changes in the mouse cortex following a soft cranial window installation

“…Supporting this inference is a study showing the effects of direct injection of IL-1β on cerebral hemodynamics and neuronal activation. 47 In that study, animals with a single intrastriatal injection of IL-1β showed decreased hemodynamics within hours of injection. In addition, local tissue oxygenation and LFP recordings also dropped within hours of injection.…”

Sensory adaptation in the barrel cortex during active sensation in the awake, behaving mouse

“…Extracellular recordings from layer 5 of barrel columns were targeted as follows: Mice were trimmed to 3 whiskers in C row (C1, C2 and C3) and intrinsic optical imaging was performed to locate the area corresponding to the targeted whisker barrel, under isoflurane anaesthesia (Bray et al, 2016). Acute implantation of a 16-channel linear silicon probe (Cambridge NeuroTech, Cambridge, United Kingdom) was performed at the beginning of each session under isoflurane anaesthesia.…”

“…Recording. Extracellular recordings from layer 5 of barrel columns were targeted as follows: Mice were trimmed to 3 whiskers in C row (C1, C2 and C3) and intrinsic optical imaging was performed to locate the area corresponding to the targeted whisker barrel, under isoflurane anaesthesia (Bray et al, 2016).…”

Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases

“…Indeed, 2D optical imaging spectroscopy [238] or optical projection tomography applied to a 3D spatial assessment of the development of neuroinflammation [239] provided positive outcomes in rodent models.…”

“…Beyond the interest of coupling MRI techniques with TSPO PET modality, recent advances in imaging of activated microglia have been shown promising results. Indeed, 2D optical imaging spectroscopy [ 238 ] or optical projection tomography applied to a 3D spatial assessment of the development of neuroinflammation [ 239 ] provided positive outcomes in rodent models.…”