Intraventricular infusion of 2-amino-7-phosphonoheptanoate (APH) mitigates ischaemic brain damage

Intracerebroventricular infusion of the competitive N-methyl-D-aspartate (NMDA) antagonist 2-amino-7-phosphonoheptanoate (APH) was evaluated as a neuroprotective regimen in a rat transient cerebral ischaemia model allowing long-term recovery. Ventricular delivery of APH via an osmotic minipump was chosen to allow continuous and direct access to brain tissue of this polar molecule, and because of the potential applicability of such a regimen in clinical situations where the brain is at risk from cerebral ischaemia and a ventricular catheter is in place. The highest tolerable concentration of APH, 50 mM, was given at 1 microliter/h. Selective neuronal necrosis was significantly reduced in the cerebral cortex and the incidence of infarction in the substantia nigra pars reticulata (SNPR) was decreased. A borderline protective effect was seen in the hippocampal CA1 pyramidal neurons, and no significant protection was seen in the caudate nucleus. The results suggest a limited usefulness for APH as a cerebral protective agent.