Vascular endothelial growth factor (VEGF) A is generated as two isoform families by alternative RNA splicing, represented by VEGF-A165a and VEGF-A165b. These isoforms have opposing actions on vascular permeability, angiogenesis, and vasodilatation. The proangiogenic VEGF-A165a isoform is neuroprotective in hippocampal, dorsal root ganglia, and retinal neurons, but its propermeability, vasodilatatory, and angiogenic properties limit its therapeutic usefulness. In contrast, a neuroprotective effect of endogenous VEGF-A165b on neurons would be advantageous for neurodegenerative pathologies. Endogenous expression of human and rat VEGF-A165b was detected in hippocampal and cortical neurons. VEGF-A165b formed a significant proportion of total VEGF-A in rat brain. Recombinant human VEGF-A165b exerted neuroprotective effects in response to multiple insults, including glutamatergic excitotoxicity in hippocampal neurons, chemotherapy-induced cytotoxicity of dorsal root ganglion neurons, and retinal ganglion cells (RGCs) in rat retinal ischemia-reperfusion injury in vivo. Neuroprotection was dependent on VEGFR2 and MEK1/2 activation but not on p38 or phosphatidylinositol 3-kinase activation. Recombinant human VEGF-A165b is a neuroprotective agent that effectively protects both peripheral and central neurons in vivo and in vitro through VEGFR2, MEK1/2, and inhibition of caspase-3 induction. VEGF-A165b may be therapeutically useful for pathologies that involve neuronal damage, including hippocampal neurodegeneration, glaucoma diabetic retinopathy, and peripheral neuropathy. The endogenous nature of VEGF-A165b expression suggests that non-isoform-specific inhibition of VEGF-A (for antiangiogenic reasons) may be damaging to retinal and sensory neurons.

The PERG, especially the PERG ratio, detected glaucoma patients 4 years before visual field changes occurred, with a sensitivity/specificity of 75%/76%. Slope analysis required multiple visits, but provided little additional information in detecting converters.

The main purpose of the present study was to investigate the effects of the neuroprotective agent riluzole on the electrically evoked release of [3H]‐glutamate ([3H]‐Glu) in mouse neocortical slices. The reported selectivity of riluzole for excitatory amino acids was tested in release experiments with further neurotransmitters. Also distinct species, mouse, rat and man were compared. [3H]‐Glu was formed endogenously during incubation of slices with [3H]‐glutamine ([3H]‐Gln). Released [3H]‐Glu and tissue [3H]‐Glu was separated by anion exchange chromatography. Electrically evoked [3H]‐Glu release was strongly diminished by tetrodotoxin (TTX) and Ca2+‐withdrawal. Riluzole (100 μM) depressed the release of [3H]‐Glu up to 77% (IC50=19.5 μM). Riluzole was also able to inhibit strongly the electrically evoked release of [3H]‐acetylcholine ([3H]‐ACh) (at 100 μM by 92%, IC50=3.3 μM, and [3H]‐dopamine ([3H]‐DA) (at 32 μM by 72%, IC50=6.8 μM). However, the release of [3H]‐serotonin ([3H]‐5‐HT) was less diminished (at 100 μM by 53%, IC50=39.8 μM). Riluzole up to 100 μM did not affect [3H]‐noradrenaline ([3H]‐NA) release. Between species, i.e. in mouse, rat and human neocortex, no significant differences between the effects of riluzole could be observed. The NMDA‐receptor blocker MK‐801 (1 μM) and the AMPA/Kainate‐receptor blocker NBQX (1 μM) did neither affect the electrically evoked [3H]‐ACh release nor its inhibition by riluzole, indicating that effects of riluzole on transmitter release were neither due to modulation of ionotropic Glu receptors, nor due to indirect inhibition of Glu release through these receptors. Taken together, riluzole inhibits the release of distinct neurotransmitters differently, but is not selective for the excitatory amino acid Glu. British Journal of Pharmacology (2000) 130, 1227–1234; doi:

NAP acts neuroprotectively in vivo after retinal ischemia and optic nerve crush, and may have potential in treating optic nerve diseases.

The amounts of reduction in VEPs, ERG, and RGCs differed as the duration of ischemia increased. The electrophysiological parameters presented in this study may serve as a useful addition to morphologic evaluations in future neuroprotection studies in vivo.