Acetazolamide Mitigates Intracranial Pressure Spikes Without Affecting Functional Outcome After Experimental Hemorrhagic Stroke

Increased intracranial pressure (ICP) after stroke can lead to poor outcome and death. Novel treatments to combat ICP rises are needed. The carbonic anhydrase inhibitor acetazolamide diminishes cerebrospinal fluid (CSF) production, reduces ICP in healthy animals, and is beneficial for idiopathic intracranial hypertension patients. We tested whether acetazolamide mitigates ICP elevations by presumably decreasing CSF volume after collagenase-induced striatal hemorrhage in rats. We confirmed that acetazolamide did not adversely affect hematoma formation in this model or physiological variables, such as temperature. Then, we assessed the effects of acetazolamide on ICP. Lastly, we tested the effects of acetazolamide on behavioral and histological outcome. Acetazolamide reduced the magnitude and occurrence of short-timescale ICP spikes, assessed as disproportionate increases in ICP (sudden ICP increases > 10 mmHg), 1-min peak ICP, and the magnitude of spikes > 20 mmHg. However, mean ICP was unaffected. In addition, acetazolamide reduced ICP variability, reflecting improved intracranial compliance. Compliance measures were strongly correlated with high peak and mean ICP, whereas ipsilateral hemisphere water content was not correlated with ICP. Despite effects on ICP, acetazolamide did not improve behavioral function or affect lesion size. In summary, we show that intracerebral hemorrhage creates an impaired compliance state within the cranial space that can result in large, transient ICP spikes. Acetazolamide ameliorates intracranial compliance and mitigates ICP spikes, but does not improve functional outcome, at least for moderate-severity ICH in rats.