The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia

• Unilateral hypoxia-ischemia (HI) was induced in C57/BL6 male mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brains, respectively. HI duration was adjusted to obtain a similar extent of brain injury at all ages. Apoptotic mechanisms (nuclear translocation of apoptosis-inducing factor, cytochrome c release and caspase-3 activation) were several-fold more pronounced in immature than in juvenile and adult brains. Necrosis-related calpain activation was similar at all ages. The CA1 subfield shifted from apoptosis-related neuronal death at P5 and P9 to necrosis-related calpain activation at P21 and P60. Oxidative stress (nitrotyrosine formation) was also similar at all ages. Autophagy, as judged by the autophagosome-related marker LC-3 II, was more pronounced in adult brains. To our knowledge, this is the first report demonstrating developmental regulation of AIF-mediated cell death as well as involvement of autophagy in a model of brain injury.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Aging/*physiology

Animals

Apoptosis/*physiology

Apoptosis Inducing Factor

Autophagy/physiology

Brain Injuries/metabolism/pathology/physiopathology

Calpain/metabolism

Caspases/metabolism

Cell Death/physiology

Cytochromes c/metabolism

Disease Models

Animal

Flavoproteins/metabolism

Hypoxia-Ischemia

Brain/metabolism/pathology/*physiopathology

Male

Membrane Proteins/metabolism

Mice

Mice

Inbred C57BL

Microtubule-Associated Proteins/metabolism

Mitochondria/metabolism

Necrosis/metabolism

Neurons/metabolism/physiology

Protein Transport

Research Support

Non-U.S. Gov't

Tyrosine/analogs & derivatives/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)