Showing papers by "Dan Lindholm published in 2001"
TL;DR: It is concluded that a treatment producing an increase in DNA fragmentation in the early phase may be compatible with an overall beneficial effect on outcome after TBI and should be considered in the screening process for future neuroprotective remedies.
Abstract: The mechanisms and role of nerve cell death after traumatic brain injury (TBI) are not fully understood. The authors investigated the effect of pretreatment with the oxygen free radical spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) on the number of neurons undergoing apoptosis after TBI in rats. Apoptotic cells were identified by the TUNEL method combined with the nuclear stain, Hoechst 33258, and immunohistochemistry for the active form of caspase-3. Numerous neurons became positive for activated caspase 3 and TUNEL in the cortex at 24 hours after injury, suggesting ongoing biochemical apoptosis. In PBN-treated rats, a significantly greater number of cells were found to be TUNEL positive at 24 hours compared with controls. However, PBN treatment resulted in a reduced cortical lesion volume and improved behavioral outcome two weeks after injury. The authors conclude that a treatment producing an increase in DNA fragmentation in the early phase may be compatible with an overall beneficial effect on outcome after TBI. This should be considered in the screening process for future neuroprotective remedies.
48 citations
TL;DR: Overexpression of Bcl-w in sympathetic neurons also counteracted death induced by NGF deprivation, which was not reduced by co-expression of either of the two Bad variants.
27 citations
TL;DR: The results show that HGF is present in normal CSF and does not appear to cross the CSF barrier significantly unless it is severely disrupted, which is unlike previous studies which have shown strong increases of HGF concentration in CSF.
24 citations
TL;DR: Investigation of the expression and distribution of XIAP mRNA and protein in rat brain using RNase protection assay in addition to Western blotting and immunohistochemistry with a specific anti-XIAP antibody shows XIAP protein was shown to be expressed in embryonic and adult brains with slightly higher levels in embryos and neonatal brains compared to adults.
Abstract: INTRODUCTION. Inhibitor of apoptosis protein (IAP) family consists of several antiapoptotic proteins conserved among species. The IAPs have a well-conserved motif of approximately 65 residues, called the baculovirus inhibitory repeat (BIR) (1). Baculovirus and drosophila IAPs have two, but most IAPs contain three BIR domains. Most of the IAPs also have a C-terminal RING domain which consists of conserved amino acids with zinc binding capacity. XIAP is one of the five known human IAPs and it binds directly and inhibits the activity of caspases (2). The BIR2 domain in XIAP is sufficient to mediate this inhibition (3). However little is known about the presence and function of XIAP in the nervous system. METHOD. In this study, we have investigated the expression and distribution of XIAP mRNA and protein in rat brain using RNase protection assay in addition to Western blotting and immunohistochemistry with a specific anti-XIAP antibody. Neuronal cell death upon kainic acid stimulation was investigated using TUNEL method and caspase-3 activation. RESULTS. Two transcripts of XIAP mRNA are present in rat brains, suggesting a heterogeneity of XIAP in the carboxyterminal region. Using a specific anti-XIAP antibody, XIAP protein was shown to be expressed in embryonic and adult brains with slightly higher levels in embryonic and neonatal brains compared to adults. There was a widespread distribution of XIAP immunoreactive cells in adult rat brains, among others in hippocampus, cortex and substantia nigra. Using double-labelling, it was shown that both neuronal and glia cells express XIAP. Kainic acid treatment is known to cause widespread neuronal cell death in hippocampus and amygdala. XIAP protein levels were increased in the hippocampus 12th and 24th after kainic acid. The intensity of XIAP staining was increased particularly in the hippocampal CA3 area. In the same area, many TUNEL positive and active caspase-3 positive cells were found. Caspase-3 is activated 24th after kainic acid in vivo and in vitro in cultured embryonic hippocampal neurons upon kainic acid stimulus. In hippocampus, XIAP does not colocalize with markers for cell death raising the possibility that XIAP is expressed in viable cells but not in dying cells. Using cultured embryonic hippocampal neurons, it was shown that XIAP becomes a target for active caspase-3 and that it is degradated into smaller pieces. DISCUSSION. XIAP mRNA is expressed in developing and adult rat brains, and the number of XIAP positive cells and XIAP protein levels were regulated by kainic acid. The largest change in XIAP immunoreactivity was observed in CA3 area, which was particularly vulnerable in this model. Labelling of cells with the TUNEL method and with antibody for
9 citations
TL;DR: The data demonstrate that ALS does not show a lack of the trophic signalling axis, HGF/MET, suggesting that the signalling system itself is not affected, and a moderate increase in HGF-secretion may represent a compensatory effect.
8 citations