Inhibition of excitatory synaptic transmission in hippocampal neurons by levetiracetam involves Zn²âº-dependent GABA type A receptor-mediated presynaptic modulation.

Levetiracetam (LEV) is an antiepileptic drug with a unique but as yet not fully resolved mechanism of action. Therefore, by use of a simplified rat-isolated nerve-bouton preparation, we have investigated how LEV modulates glutamatergic transmission from mossy fiber terminals to hippocampal CA3 neurons. Action potential-evoked excitatory postsynaptic currents (eEPSCs) were recorded using a conventional whole-cell patch-clamp recording configuration in voltage-clamp mode. The antiepileptic drug phenytoin decreased glutamatergic eEPSCs in a concentration-dependent fashion by inhibiting voltage-dependent Na⁺ and Ca²âº channel currents. In contrast, LEV had no effect on eEPSCs or voltage-dependent Na⁺ or Ca²âº channel currents. Activation of presynaptic GABA type A (GABA(A)) receptors by muscimol induced presynaptic inhibition of eEPSCs, resulting from depolarization block. Low concentrations of Zn²âº, which had no effect on eEPSCs, voltage-dependent Na⁺ or Ca²âº channel currents, or glutamate receptor-mediated whole cell currents, reduced the muscimol-induced presynaptic inhibition. LEV applied in the continuous presence of 1 µM muscimol and 1 µM Zn²âº reversed this Zn²âº modulation on eEPSCs. The antagonizing effect of LEV on Zn²âº-induced presynaptic GABA(A) receptor inhibition was also observed with the Zn²âº chelators Ca-EDTA and RhodZin-3. Our results clearly show that LEV removes the Zn²âº-induced suppression of GABA(A)-mediated presynaptic inhibition, resulting in a presynaptic decrease in glutamate-mediated excitatory transmission. Our results provide a novel mechanism by which LEV may inhibit neuronal activity.

Effective use of flow-spoiled FBI and time-SLIP methods in the diagnostic study of an aberrant vessel of the head and neck: "left jugular venous steal by the right jugular vein".

Three-dimensional (3D) time-of-flight (TOF) is now commonly used in routine magnetic resonance angiography (MRA) studies of the head and neck. However, there are limits to its diagnostic abilities in the clinical field and, in some instances, a more invasive supplementary examination may be required. We incidentally discovered a patient with an aberrant vessel of the head and neck that ran alongside the left carotid artery and contained a constant, slowly pulsating efferent blood flow. 3D-TOF and carotid ultrasonography could not determine the nature and origin of this vessel. Additional studies using flow-spoiled fresh blood imaging (flow-spoiled FBI) and time spatial labeling inversion pulse (time-SLIP) methods were effective in determining that the vessel was the left jugular vein, and that the continuous venous reflux was a result of a venous steal by the right jugular vein. We show that by combining different MRA techniques we can effectively achieve diagnosis without resorting to more invasive examinations.

Influence of ischemic preconditioning on levels of nerve growth factor, brain-derived neurotrophic factor and their high-affinity receptors in hippocampus following forebrain ischemia.

Preconditioning of gerbil brain with a sublethal forebrain ischemia is known to protect hippocampal CA1 neurons following a subsequent lethal ischemia (the second ischemia) which usually damages neurons (ischemic tolerance). Present report using a confocal laser scanning microscope demonstrated that the hippocampal cells of sham operation gerbils contained immunofluorescent NGF and BDNF and their high-affinity receptors (TrkA and TrkB). A 2-min ischemia caused little change of these proteins (ANOVA test, P<0.05). After the second lethal ischemia, in the CA1 area with ischemic preconditioning (2-min ischemia), only BDNF but not NGF and their high-affinity receptors showed a transient reduction at 4 h (ANOVA test, P<0.01) and improved from 1 day (ANOVA test, P<0.05). In the CA1 area without ischemic preconditioning (sham operation), NGF and its high-affinity TrkA receptor showed a consistent reduction from 4 h to 7 days (ANOVA test, P<0.05); BDNF and TrkB decreased transiently from 4 h to 1 day (ANOVA test, P<0.05) but were recovered in the surviving neurons from 3 days. At 3 and 7 days after the second lethal ischemia, apoptotic cell injury could be seen in the CA1 area without ischemic preconditioning but was sparsely noted in the CA1 area with ischemic preconditioning. In the ischemia-resistant CA3 and dentate gyrus areas, only BDNF decreased significantly at 7 days in the CA3 area without ischemic preconditioning (ANOVA test, P<0.01). However, no significant change occurred in NGF, TrkA and TrkB immunofluorescence from 4 h to 7 days after the second lethal ischemia in the CA3 and dentate gyrus areas with and without ischemic preconditioning. Western blot study showed that in the hippocampal formation with ischemic preconditioning, preconditioning prevented the decline of these protein levels from 1 day to 7 days after the second lethal ischemia (ANOVA test, P>0.05). Results of this study demonstrate that ischemic preconditioning recovers the initial decline in NGF and BDNF and their corresponding receptors in the vulnerable CA1 neurons after the second lethal ischemia, suggesting that growth factors might play a role in the protective mechanism of ischemic preconditioning.

The dawn of a new era for stroke treatment.

Due to two developments that have taken place within the past few years, the treatment for stroke is about to change immensely. First, it has become possible to significantly inhibit the spread of hypoperfusive tissue damage by initiating antioxidant therapy within 24 hours of a stroke. As a result of this new therapy, many physicians now feel that the prognosis for stroke patients has improved considerably. Second, elucidation of the brain function of post-stroke rehabilitation has made headway as advanced functional brain imaging techniques have provided reliable data, thereby substantiating new rationales.