Cerebral edema is a common cause of death after ischemic stroke. The initial cytotoxic phase occurs secondary to ATP depletion resulting in the accumulation of Na⁺ from the extracellular space inside cells causing them to swell. This leads to the ionic phase consisting of the net gain of Na⁺ and water from external sources across an intact BBB. We therefore evaluated if CSF is a potential external source of Na⁺and water that could facilitate cytotoxic and ionic edema. 

To determine if cerebrospinal fluid (CSF) is a source of edema fluid after acute ischemic stroke and cardiac arrest.

Focal or global cerebral ischemia was induced in mice using microsphere permanent middle artery occlusion (MCAO) or asphyxial cardiac arrest (CA), respectively. Edema was quantified by calculating brain water content at different time-points after ischemia. Transport of CSF within the brain was analyzed using transcranial imaging and dynamic contrast-enhanced MRI. ²²Na and ³H-mannitol were delivered into CSF or plasma to assess Na⁺sources. The onset of cytotoxic edema was evaluated using Glt1-GCaMP7mice and ADC maps from diffusion-weighted MRI. Volume changes of CSF were analyzed using 3D-FIESTA. 

Immediately after MCAO and CA, there is a rapid entry of CSF into the brain along perivascular spaces following the distribution of the glymphatic pathway within the first 5 min. This influx resulted in the increase of brain water content with most Na⁺ ions originating from the CSF and not plasma. The timing of CSF entry occurred shortly after cortical spreading depolarizations as seen with calcium imaging and decreased ADC. Using 3D-FIESTA, we observed CSF being absorbed into the tissue immediately following ischemia. 

CSF is an important contributor to edema formation after acute focal and global stroke. Further work is needed to determine whether this prevents or ameliorates the development of the later stages of cerebral edema.