ABSTRACT
Injury ........................................................................................... 182 11.2.4 Cell Protector or Attacker? Knockouts Highlight
Neuropeptides’ Dual Role ............................................................ 182 11.2.5 Cell Death by Necrosis and Apoptosis ........................................ 183
11.3 Neuroprotectant VIP................................................................................... 183 11.4 PACAP Protection in Neuronal Systems .................................................... 185
11.4.1 Retina ............................................................................................ 185 11.4.2 Cerebellum ................................................................................... 186 11.4.3 Hippocampus and Cortex ............................................................. 188 11.4.4 Dopaminergic Neurons ................................................................ 190 11.4.5 Damage to Axons, Spinal Cord, Peripheral Neurons ................... 190
11.5 PACAP Protection in Nonneuronal Systems .............................................. 191 11.5.1 Heart ............................................................................................. 191 11.5.2 Kidney .......................................................................................... 192 11.5.3 Immune System in Sepsis and Autoimmunity ............................. 192
Neuropeptides have been implicated in both the mitigation and exacerbation of cellular injury from ischemia, physical trauma, inammation, and excitotoxicity and other physiological insults found in a wide variety of neurodegenerative diseases. One such dual-purpose neuropeptide is substance P, shown to exacerbate neuronal cell death in hippocampus after seizure [1] and yet to be neuroprotective in striatum in vivo [2, 2a] and in cultured cerebellar [3] and striatal [4] neurons. Of the opioid peptides, dynorphin is neurodamaging in vivo (Hauser this volume), whereas others can, with pharmacological preconditioning, mediate neuroprotection. The expression of two other neuropeptides, neuropeptide Y (NPY) and adrenomedullin (AM), are greatly increased after neurotrauma. NPY, which appears to help regulate the migration of neuroprogenitor cells into the hippocampus, is highly upregulated following hippocampus damage in rodent models of epilepsy [5, 6]. AM, which is dramatically upregulated after striatal ischemia and reperfusion, appears to be neuroprotective after central nervous system (CNS) injury [7].
