The effect of a global birth asphyxia on the ontogeny of BDNF and NGF protein expression in the juvenile brain.
Neurotrophic growth factors are strongly upregulated following brain injury in order to limit the amount of delayed apoptotic cell death. In particular, the neurotrophins NGF and BDNF are upregulated following injury and offer neuroprotection when administered after brain injury. Further, both growth factors are involved in the control of neural proliferation and plasticity during both development and recovery from injury. We used a model of global birth asphyxia in the rat to follow the ontogeny of BDNF and NGF protein levels within the normal and asphyctic hippocampus and cerebellum for the first 28 days of postnatal life. In contrast to what is seen in the injured adult brain, we see an early and long lasting decrease in NGF content within the asphyctic hippocampus, whereas cerebellar NGF content showed a delayed increase following asphyxia. Asphyxia also caused a delayed increase in BDNF content within the hippocampus but decreased BDNF levels within the cerebellum. Further, a comparison of the ontogeny of plasma corticosterone over development shows that endogenous BDNF protein levels are not sensitive to the dramatic increase in circulating corticosterone that occurs at the end of the stress hyporesponsive period. In summary, we find that perinatal birth asphyxia causes opposing changes in NGF and BDNF protein expression in a spatio-temporal-dependent manner. These results point to the need for more detailed studies on the mechanisms of action of BDNF and NGF within the developing brain before these can be used therapeutically following birth asphyxia in man.
Scheepens
Arjan
A
Department of Pediatrics, GROW Research Institute, Universiteit of Maastricht, Maastricht, The Netherlands. a.sheepens@np.unimaas.nl
Wassink
Guido
G
Blanco
Carlos E
CE
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D019208:Brain-Derived Neurotrophic Factor; D020932:Nerve Growth Factor