title: Increased neurogenesis after hypoxic-ischemic encephalopathy in humans is age related.
abstract: The leading cause of morbidity and mortality after successful resuscitation is hypoxic-ischemic encephalopathy (HIE), which results in neuronal loss within the neocortex and the hippocampal formation. This study focuses on the impact of HIE on adult neurogenesis in the human hippocampal dentate gyrus as a potential intrinsic regenerative mechanism in response to neuronal damage. Brain sections of 22 autopsy cases with HIE and of 19 age-matched controls without neuropathological abnormalities were investigated by means of immunohistochemistry. The densities of immature granule cells during axon guidance and outgrowth (assessed by TUC-4 immunohistochemistry) and of young calretinin-expressing postmitotic neurons were increased in the granule cell layer of cases who had suffered from HIE (P = 0.0002 and P = 0.0001, respectively). Similarly, the density of apoptotic granule cells, as detected by in situ tailing and morphological criteria, was increased in HIE (P = 0.014). In cases with HIE, the increase in the density of TUC-4-labeled cells inversely correlated with age (P = 0.027). In contrast, neither the density of proliferating nor that of apoptotic cells was substantially influenced by age within the control group. Taken together, both an increase in adult neurogenesis and in neuronal apoptosis was observed in the human dentate gyrus in response to HIE. The data suggest a decrease of adult neurogenesis in older-aged cases. Whether neurogenesis can contribute to recovery after HIE remains to be determined. The stimulation of adult neurogenesis may be less efficient in older victims of HIE.
authors.affiliation: Department of Neurology, Georg-August-University, Göttingen, Germany.
authors.forename: Wulf-Rainer C
authors.initials: WR
authors.lastname: Mattiesen
authors.forename: Simone C
authors.initials: SC
authors.lastname: Tauber
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerber
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bunkowski
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001344:Autopsy; D064032:Calbindin 2; D016022:Case-Control Studies; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis; D055495:Neurogenesis; D009474:Neurons / Q000737:chemistry / Q000473:pathology*; D012189:Retrospective Studies; D064030:S100 Calcium Binding Protein G / Q000032:analysis
chemical_list: C576764:CALB2 protein, human; D064032:Calbindin 2; C102926:DPYSL3 protein, human; D009124:Muscle Proteins; D064030:S100 Calcium Binding Protein G