Mitochondrial injury has been implicated in ischemic neuronal injury. Mitochondria, producing adenosine triphosphate by virtue of electron flow, have been shown to be both the sites of superoxide anion (O2-) production and the target of free radical attacks. We evaluated these mechanisms in an in vivo cerebral ischemia model, using mutant mice with a heterozygous knock-out gene (Sod2 -/+) encoding mitochondrial manganese superoxide dismutase (Mn-SOD). Sod2 -/+ mice demonstrated a prominent increase in O2- production under normal physiological conditions and in ischemia, as evidenced by specific oxidation of a fluorescent probe, hydroethidine, reflecting decreased activity of Mn-SOD. A mitochondrial viability assay that used rhodamine 123, which is accumulated by transmembrane potential of viable mitochondria, demonstrated accelerated development of mitochondrial injury. This rapid progress of ischemic injury resulted in exacerbation of infarct size and hemisphere enlargement, causing advanced neurological deficits but without altering DNA fragmentation induction. The present study suggests that O2- overproduced in a mitochondrial compartment, when uncoupled from antioxidant defenses, induces impairment of mitochondrial function and causes exacerbation of cerebral infarction after ischemia.

Myelin is the lipoprotein multimembrane that functions as an insulator preventing the flow of ion currents across the axonal membrane and facilitating the conduction of nerve impulses. It is synthesized by oligodendrocytes in the central nervous system at about the time of birth in mammals. During the initial stages of myelination, several proteins are phosphorylated on tyrosine. Among these proteins, we identified Fyn tyrosine kinase, one of the non-receptor-type tyrosine kinases of the Src family. Here we report that Fyn tyrosine kinase is activated during the initial stages of myelination and that it is associated with the large myelin-associated glycoprotein (MAG), an adhesion molecule that has been implicated in myelinogenesis. The Fyn-large MAG association requires amino-terminal domains of Fyn that include SH2 and SH3 (Src homology domains 2 and 3). Crosslinking of large MAG with antibody induces a rapid increase in the specific activity of Fyn kinase. These results indicate that Fyn participates in the initial events of myelination as a signalling molecule downstream of large MAG; indeed, we find that fyn-deficient mice exhibit impaired myelination.

We report 2 patients with Guillain-Barré syndrome (GBS) following Campylobacter jejuni enteritis. Electrophysiologic studies indicated that the predominant process was axonal degeneration of motor nerves, and clinical recovery was poor. Serum testing by thin-layer chromatography and enzyme-linked immunosorbent assay revealed that the sera from both patients contained high titers of IgG antibody against GM1 ganglioside. These cases may represent a subgroup of GBS as acute axonal polyneuropathy following C jejuni enteritis associated with anti-GM1 antibodies.

This article represents the update of ‘European Stroke Initiative Recommendations for Stroke Management’, first published in this Journal in 2000. The recommendations are endorsed by the 3 European societies which are represented in the European Stroke Initiative: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.

We used the enzyme-linked immunosorbent assay to investigate autoantibodies against the gangliosides GM1, GD1a, GD1b, GT1b, GD2, and GQ1b in sera from 16 patients with Fisher's syndrome. We found high anti-GQ1b antibody titers, mainly those of the IgG class, in the sera of 13 of these patients. The titers decreased with the clinical course of the illness. Moreover, anti-GQ1b antibody-positive patients had more severe ataxia of cerebellar type than the antibody-negative patients.

No abstract

Summary: Excitotoxicity is implicated in the pathogenesis of several neurologic diseases, such as chronic neurodegenerative diseases and stroke. Recently, it was reported that excitotoxic ity has a relationship to apoptotic neuronal death, and that the mitochondrial toxin, 3-nitropropionic acid (3-NP), could in duce apoptosis in the striatum. Although striatal lesions pro duced by 3-NP could develop through an excitotoxic mecha nism, the exact relationship between apoptosis induction and excitotoxicity after 3-NP treatment is still not clear. The authors investigated the role of excitotoxicity and oxidative stress on apoptosis induction within the striatum after intraperitoneal in jection of 3-NP. The authors demonstrated that removal of the corticostriatal glutamate pathway reduced superoxide produc tion and apoptosis induction in the denervated striatum of deExcitotoxicity related to mitochondrial dysfunction and free radical-induced oxidative damage has been im plicated in the pathogenesis of several neurobiologic dis orders, such as ischemic neuronal injury and chronic neurodegenerative diseases (Beal, 1992; Dugan et aI., 1995). Traditionally, excitotoxic neuronal cell death has been considered to be necrotic in nature, but recent stud ies suggest that apoptotic cell death may have a role in

Incubation of highly purified human myelin at 25" and pH 8 in ammonium bicarbonate buffer resulted in the conversion of the myelinassociated glycoprotein (MAG) to a smaller derivative (dMAG) with an apparent molecular weight about 10,000 less. dMAG was stable and was not degraded to lower-molecular-weight breakdown products. Incubation of myelin under these conditions also resulted in the degradation of basic protein, but at a much slower rate. Half of the MAG was converted to dMAG in about 30 min, whereas degradation of half of the basic protein required 18 h of incubation. There was no significant loss of proteolipid, the Wolfgram doublet, or other myelin proteins during incubation for up to 18 h under these conditions. The formation of dMAG and the degradation of basic protein appear to be mediated by similar enzymatic activities; both processes exhibited broad pH optima in the neutral range, were prevented by briefly heating the myelin to 70" before incubation, and were stimulated by ammonium bicarbonate and other salts. Incubation of purified rat myelin also resulted in the formation of dMAG and the degradation of basic protein, but the conversion to dMAG occurred much more slowly than in human myelin preparations. In the rat, the percentage decreases in intact MAG and in basic protein were similar to each other and proceeded at rates comparable to the loss of basic protein in human myelin. These studies confirm and extend earlier demonstrations of neutral protease activity in purified myelin, and show that cleavage of MAG is one of the effects of this activity. The proteolytic activity affecting MAG and basic protein was not significantly reduced by further purification of the myelin on sucrose or CsCl gradients, suggesting that the neutral protease may be a myelin-related enzyme. The very high susceptibility of human MAG to this enzyme indicates that the effect of neutral protease on this glycoprotein should be considered in connection with demyelinating diseases. Key Words: Myelin-Protease-Glycoprotein-Basic protein-Myelin-associated glycoprotein. Sato S. et al. Susceptibility of the myelin-associated glycoprotein and basic protein to a neutral protease in highly purified myelin from human and rat brain. J. Neurochem. 39, 97-105 (1982).The myelin-associated glycoprotein (MAG) is a quantitatively minor constituent of purified myelin , which has recently been shown to be selectively localized in the periaxonal portion of myelin sheaths (Sternberger et al., 1979). Immunocytochemistry and radioimmunoassay have demonstrated that MAG is lost early in the development of multiple sclerosis plaques (Itoyama et al., 1980;Johnson et al., 1981). In the course of isolating MAG from human white matter for chemical characterization, it was observed that MAG was sometimes converted to a lower-molecular-weight