Premium
D ‐β‐hydroxybutyrate is neuroprotective against hypoxia in serum‐free hippocampal primary cultures
Author(s) -
Masuda R.,
Monahan J.W.,
Kashiwaya Y.
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20464
Subject(s) - trypan blue , penumbra , neuroprotection , poly adp ribose polymerase , propidium iodide , apoptosis , hippocampal formation , hypoxia (environmental) , cytochrome c , chemistry , lactate dehydrogenase , ketone bodies , programmed cell death , endocrinology , medicine , microbiology and biotechnology , biochemistry , biology , polymerase , ischemia , metabolism , enzyme , oxygen , organic chemistry
Hypoxia decreased survival of cultured rat primary hippocampal neurons in a time dependent manner. Addition of 4 mM Na D ‐β‐hydroxybutyrate (bHB), a ketone body, protected the cells for 2 hr and maintained the increase in survival compared to that of controls for up to 6 hr. Trypan blue exclusion indicated that acute cell death was reduced markedly after 2‐hr exposure to hypoxia in the bHB‐treated group. The presence of bHB also decreased the number of neurons exhibiting condensed nuclei visualized by propidium iodide, indicative of apoptosis. The mitochondrial transmembrane potential ( E m/c ) was maintained for up to 2 hr exposure to hypoxia in the bHB‐treated group, whereas the potential in the control group was decreased. Furthermore, cytochrome C release, caspase‐3 activation, and poly (ADP‐ribose) polymerase (PARP) cleavage were decreased in the bHB‐treated group for the first 2 hr of exposure. These findings indicate that ketone bodies may be a candidate for widening the therapeutic window before thrombolytic therapy and at the same time decreasing apoptotic damage in the ischemic penumbra. © 2005 Wiley‐Liss, Inc.