Oxygen metabolism,electrophysiological activity and cerebral blood flow in rat sensory cortex

Introduction

The mechanisms underlying the coupling between neuronal activation and changes in cerebral metabolism and cerebral blood flow (CBF) are still incompletely understood. There is still a debate regarding the relation of increases in cerebral metabolic rate of oxygen (CMRO2) and CBF changes during functional activation. We here examined the influence of infraorbital nerve stimulation on the relationship between oxygen metabolism, synaptic activity and CBF in rat sensory cortex. Our working hypothesis was that attenuation of the evoked CBF responses would unmask the initial dip in the tissue oxygen tension produced by increases in synaptic activity. This was based on the assumption that increases in CBF during activation clouds the initial dip by acutely increasing oxygen supply to the tissue.

Methods

Partial pressure of tissue oxygen (tpO2) was measured using a Clark-type O2 microelectrode (tip diameter between 3–4 μm). CBF was recorded by laser-Doppler flowmetry. Electrophysiological recordings of local field potentials and spike activity were made using glass microelectrodes. All experiments were carried out using an open cranial window preparation in isoflurane and α-chloralose anaesthetized adult male Wistar rats. We used stimulation trains of 4 s duration at increasing frequencies from 0.25 to 6 Hz at 1.5 mA. Evoked CBF responses were attenuated by the combined use of nitric oxide synthase (NOS) inhibition with 7-Nitroindazole (7-NI) and the non-selective cyclooxygenase (COX1 and COX2) inhibitor (Indomethacin, INDO).

Results

Stimulation consistently increased synaptic excitatory activity as evidenced by an increase in the summed LFP amplitudes (ΣLFP). At the same time CBF increased frequency-dependently. The stimulus-induced tpO2 responses were extremely variable. The changes in tpO2 often consisted only of a positive peak, on other occasions the tpO2 responses were biphasic with both an initial decrease in tissue pO2 followed by a longer lasting positive peak. Pure oxygen dips were not observed. 7NI and INDO significantly attenuated the evoked CBF responses and the positive peak of the pO2 signals. Surprisingly, abolition of the CBF responses did not enhance or produce oxygen ‘dips’. In contrast, negative tpO2 signals, if present before drug treatment, were attenuated.

Conclusion

The initial ‘dip’ of tpO2 in the sensory cortex is independent of the accompanying rise in CBF. In comparison, oxygen ‘dips’ are common in the cerebellar cortex, and in this brain region changes in tpO2 depends strongly on CBF. This may point to differences in capacity and regulation of oxygen consumption among brain regions.