Monoclonal leukocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats

Area of Science:

• Neuroscience
• Immunology
• Cardiovascular Research

Background:

• Transient focal cerebral ischemia can lead to significant brain injury.
• Leukocyte activation and infiltration are implicated in ischemic brain damage.
• Monoclonal antibody 60.3 (MoAb 60.3) targets the CDw18 leukocyte antigen complex, inhibiting leukocyte function.

Purpose of the Study:

• To investigate if inhibiting leukocyte function with MoAb 60.3 improves electrophysiological recovery.
• To determine if MoAb 60.3 decreases brain injury volume following transient focal cerebral ischemia.
• To test the hypothesis that MoAb 60.3 provides neuroprotection in a feline model of stroke.

Main Methods:

• Feline model of transient focal cerebral ischemia (90 min occlusion, 180 min reperfusion).
• Administration of MoAb 60.3 (n=8) or placebo (n=10) at 45 minutes of ischemia.
• Assessment of blood flow, somatosensory evoked potentials, and infarct volume (2,3,5-triphenyltetrazolium chloride staining).

Main Results:

• Ischemia reduced cortical blood flow; reperfusion led to hyperemia in some regions, with no group differences.
• Somatosensory evoked potentials showed no significant recovery in either group.
• Left hemispheric injury volume was similar between MoAb 60.3 treated and placebo groups (37% vs. 38%).

Conclusions:

• Inhibition of leukocyte function using MoAb 60.3 does not protect against severe focal cerebral ischemia and reperfusion injury in cats.
• The CDw18 leukocyte antigen complex may not be a critical therapeutic target for acute ischemic stroke in this model.
• Further research is needed to explore alternative neuroprotective strategies.