The pituitary
adenylate cyclase-activating
peptide (
PACAP) is involved in many processes of the developing and mature central nervous system, such as proliferation, differentiation, apoptosis, neurotransmission,
inflammation and neuroprotection. Alternative posttranslational processing of
PACAP results in two biologically active, amidated 27- and 38-amino
acid peptides termed
PACAP27 and
PACAP38. In the present study, we examined whether
traumatic brain injury (TBI) affects cellular immunopositivity for
PACAP27 and
PACAP38. Patients (n = 55) were classified into three groups dependent on their survival time (under 24 h, between 24 h and 7 days and between 7 days and 99 days postinjury).
PACAP27 and
PACAP38 were expressed by neurons and glial cells in normal human neocortex (n = 10). Following TBI, the total number of PACAP27- and PACAP38-positive cells was significantly decreased for a prolonged survival period within the traumatized neocortex. In the pericontusional cortex, the number of cells expressing
PACAP27 and
PACAP38 was significantly increased at all survival times examined. Triple immunofluorescence examinations revealed a significant increase in the absolute numbers of GFAP-positive reactive astrocytes as well as a decrease in the CNP-positive oligodendrocytes, each coexpressing
PACAP27 or
PACAP38 in the contusional and pericontusional cortex. We hypothesize that the increase of glial
PACAP immunoreactivity may be interpreted as part of a complex endogenous neuroprotective response in the pericontusional regions, but the precise role of
PACAP following TBI is yet to be determined.