Converging effects of Ginkgo biloba extract at the level of transmitter release, NMDA and sodium currents and dendritic spikes.

In this study, an attempt was made to integrate the effects of GINKGO BILOBA extract (GBE) in different experimental systems (IN VITRO cochlea, brain slice preparations and cortical cell culture) to elucidate whether these processes converge to promote neuroprotection or interfere with normal neural function. GBE increased the release of dopamine in the cochlea. NMDA-evoked currents were dose-dependently inhibited by rapid GBE application in cultured cortical cells. GBE moderately inhibited Na+ channels at depolarised holding potential in cortical cells. These inhibitory effects by GBE may sufficiently contribute to the prevention of excitotoxic damage in neurons. However, these channels also interact with memory formation at the cellular level. The lack of effect by GBE on dendritic spike initiation in neocortical layer 5 pyramidal neurons indicates that the integrative functions may remain intact during the inhibitory actions of GBE.

Traumatic axonal injury in the perisomatic domain triggers ultrarapid secondary axotomy and Wallerian degeneration.

Traumatic axonal injury (TAI) arising from diffuse brain injury (DBI) results in focally impaired axonal transport with progressive swelling and delayed disconnection over several hours within brainstem axons. Neocortical DBI-mediated perisomatic axotomy does not result in neuronal death, suggesting that a comparably delayed axotomy progression was responsible for this unanticipated response. To evaluate delayed perisomatic axotomy, the current study was initiated. Rats received intracerebroventricular 10-kDa dextran followed by moderate midline/central fluid percussion injury (FPI) or FPI alone. At 15, 30, 60, and 180 min post-injury, light and transmission electron microscopy identified impaired axonal transport via antibodies targeting amyloid precursor protein (APP), while double-label fluorescent microscopy explored concomitant focal axolemmal alterations via dextran-APP co-localization. At 15 min post-injury, perisomatic TAI was identified with LM within dorsolateral and ventral posterior thalamic nuclei. Using TEM, many sustaining somata and related proximal/distal axonal segments revealed normal ultrastructural detail that was continuous with focal axonal swellings characterized by cytoskeletal and organelle pathology. In other cases, axotomy was confirmed by loss of axonal continuity distal to the swelling. By 30 min post-injury, perisomatic axotomy predominated. By 60-180 min, somatic, proximal axonal segment, and swelling ultrastructure were comparable to earlier time points although swelling diameter increased. Distal axonal segment ultrastructure now revealed the initial stages of Wallerian degeneration. The site of perisomatic axotomy did not internalize dextran, suggesting that its pathogenesis occurred independent of altered axolemmal permeability. Collectively, this DBI-mediated ultrarapid perisomatic axotomy and its sequelae further illustrate the varied axonal responses to trauma.