Optimization of direct cortical stimulation using tibial versus median nerve sensory mapping during midline brain tumor resection: illustrative case.

Background: During brain tumor resection, neurophysiological mapping and monitoring help surgeons locate, characterize, and functionally assess eloquent brain areas in real time. The selection of mapping and monitoring targets has implications for successful surgery. Here, the authors compare direct cortical stimulation (DCS) as suggested by median nerve (MN) with posterior tibial nerve (PTN) cortical sensory mapping (SM) during mesial lesion resection.

A broad and variable lumbosacral myotome map uncovered by foraminal nerve root stimulation.

Objective: The human myotome is fundamental to the diagnosis and treatment of neurological disorders. However, this map was largely constructed decades ago, and its breadth, variability, and reliability remain poorly described, limiting its practical use.

Methods: The authors used a novel method to reconstruct the myotome map in patients (n = 42) undergoing placement of dorsal root ganglion electrodes for the treatment of chronic pain.

Safety analysis and complications of condylar screws in a single-surgeon series of 250 occipitocervical fusions.

Objective: Condylar screw fixation is a rescue technique and an alternative to the conventional configuration of occipitocervical fusion. Condylar screws are utilized when previous surgical bone removal along the supraocciput has occurred which makes anchoring of a traditional barplate technically difficult or impossible. However, the challenging dissection of C0-1 necessary for condylar screw fixation and the concerns about possible complications have, thus far, prevented the acquisition of large surgical series utilizing occipital condylar screws.

Electromyographic assessment of condylar screw placement during occipitocervical fusion.

Objective: This is a retrospective study of a series of occipitocervical fusion procedures with condylar screw fixation in which the authors investigated the utility of electromyography (EMG, free-running and triggered) as a reliable tool in assessing the positioning of condylar screws. This series consisted of 197 patients between 15 and 60 years of age who presented with craniocervical instability, and who were treated between October 2014 and December 2017.

Methods: Intraoperative free-running EMG was observed at the placement of condylar screws, as well as at realigning of the spine.

Pallidal deep brain stimulation for DYT6 dystonia.

Background: Mutations of the THAP1 gene were recently shown to underlie DYT6 torsion dystonia. Little is known about the response of this dystonia subtype to deep brain stimulation (DBS) at the internal globus pallidus (GPi).

Methods: Retrospective analysis of the medical records of three DYT6 patients who underwent pallidal DBS by one surgical team.

Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S.

PARK8/LRRK2 (leucine-rich repeat kinase 2) was recently identified as a causative gene for autosomal dominant Parkinson's disease (PD), with LRRK2 mutation G2019S linked to the most frequent familial form of PD. Emerging in vitro evidence indicates that aberrant enzymatic activity of LRRK2 protein carrying this mutation can cause neurotoxicity. However, the physiological and pathophysiological functions of LRRK2 in vivo remain elusive.

Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling.

Hydrogen peroxide (H(2)O(2)) is emerging as a ubiquitous small-molecule messenger in biology, particularly in the brain, but underlying mechanisms of peroxide signaling remain an open frontier for study. For example, dynamic dopamine transmission in dorsolateral striatum is regulated on a subsecond timescale by glutamate via H(2)O(2) signaling, which activates ATP-sensitive potassium (K(ATP)) channels to inhibit dopamine release. However, the origin of this modulatory H(2)O(2) has been elusive.

Mobilization of calcium from intracellular stores facilitates somatodendritic dopamine release.

Somatodendritic dopamine (DA) release in the substantia nigra pars compacta (SNc) shows a limited dependence on extracellular calcium concentration ([Ca(2+)](o)), suggesting the involvement of intracellular Ca(2+) stores. Here, using immunocytochemistry we demonstrate the presence of the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) that sequesters cytosolic Ca(2+) into the endoplasmic reticulum (ER), as well as inositol 1,4,5-triphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) in DAergic neurons. Notably, RyRs were clustered at the plasma membrane, poised for activation by Ca(2+) entry.

AMPA receptor-dependent H2O2 generation in striatal medium spiny neurons but not dopamine axons: one source of a retrograde signal that can inhibit dopamine release.

Dopamine-glutamate interactions in the striatum are critical for normal basal ganglia-mediated control of movement. Although regulation of glutamatergic transmission by dopamine is increasingly well understood, regulation of dopaminergic transmission by glutamate remains uncertain given the apparent absence of ionotropic glutamate receptors on dopaminergic axons in dorsal striatum. Indirect evidence suggests glutamatergic regulation of striatal dopamine release is mediated by a diffusible messenger, hydrogen peroxide (H2O2), generated downstream from glutamatergic AMPA receptors (AMPARs).

The glial antioxidant network and neuronal ascorbate: protective yet permissive for H(2)O(2) signaling.

Increasing evidence implicates reactive oxygen species, particularly hydrogen peroxide (H(2)O(2)), as intracellular and intercellular messengers in the brain. This raises the question of how the antioxidant network in the brain can be sufficiently permissive to allow messages to be conveyed yet, at the same time, provide adequate protection against oxidative damage. Here we present evidence that this is accomplished in part by differential antioxidant compartmentalization between glia and neurons.

Regulation of postsynaptic Ca2+ influx in hippocampal CA1 pyramidal neurons via extracellular carbonic anhydrase.

Synchronous neural activity causes rapid changes of extracellular pH (pH(e)) in the nervous system. In the CA1 region of the hippocampus, stimulation of the Schaffer collaterals elicits an alkaline pH(e) transient in stratum radiatum that is limited by extracellular carbonic anhydrase (ECA). When interstitial buffering is diminished by inhibition of ECA, the alkalosis is enhanced and NMDA receptor (NMDAR)-mediated postsynaptic currents can be augmented.

H2O2 signaling in the nigrostriatal dopamine pathway via ATP-sensitive potassium channels: issues and answers.

The role of reactive oxygen species (ROS) as signaling agents is increasingly appreciated. Studies of ROS functions in the central nervous system, however, are only in their infancy. Using fast-scan cyclic voltammetry and fluorescence imaging in brain slices, the authors discovered that hydrogen peroxide (H2O2) is an endogenous regulator of dopamine release in the dorsal striatum.

Limited regulation of somatodendritic dopamine release by voltage-sensitive Ca channels contrasted with strong regulation of axonal dopamine release.

The mechanism underlying somatodendritic release of dopamine (DA) appears to differ from that of axon-terminal release. Specifically, somatodendritic DA release in the substantia nigra pars compacta (SNc) persists in low extracellular Ca2+ concentrations that are insufficient to support axonal release in striatum, suggesting that limited Ca2+ entry is necessary to trigger somatodendritic release. Here, we compared the role of voltage-dependent Ca2+ channels in mediating DA release in striatum versus SNc using specific blockers of N-, P/Q-, T-, R- and L-type Ca2+ channels individually and in combination.

Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, not ATP depletion.

Mitochondrial dysfunction is a potential causal factor in Parkinson's disease. We show here that acute exposure to the mitochondrial complex I inhibitor rotenone (30-100 nM; 30 min) causes concentration-dependent suppression of single-pulse evoked dopamine (DA) release monitored in real time with carbon-fiber microelectrodes in guinea pig striatal slices, with no effect on DA content. Suppression of DA release was prevented by the sulfonylurea glibenclamide, implicating ATP-sensitive K+ (KATP) channels; however, tissue ATP was unaltered.

Endogenous hydrogen peroxide regulates the excitability of midbrain dopamine neurons via ATP-sensitive potassium channels.

ATP-sensitive K+ (K(ATP)) channels link metabolic state to cell excitability. Here, we examined regulation of K(ATP) channels in substantia nigra dopamine neurons by hydrogen peroxide (H2O2), which is produced in all cells during aerobic metabolism. Blockade of K(ATP) channels by glibenclamide (100 nM) or depletion of intracellular H2O2 by including catalase, a peroxidase enzyme, in the patch pipette increased the spontaneous firing rate of all dopamine neurons tested in guinea pig midbrain slices.

Activation of ATP-sensitive K+ (K(ATP)) channels by H2O2 underlies glutamate-dependent inhibition of striatal dopamine release.

In many cells, ATP-sensitive K+ channels (KATP channels) couple metabolic state to excitability. In pancreatic beta cells, for example, this coupling regulates insulin release. Although KATP channels are abundantly expressed in the brain, their physiological role and the factors that regulate them are poorly understood.

Brain edema induced by in vitro ischemia: causal factors and neuroprotection.

Decreased cerebral blood flow, hence decreased oxygen and glucose, leads to ischemic brain injury via complex pathophysiological events, including excitotoxicity, mitochondrial dysfunction, increased intracellular Ca2+, and reactive oxygen species (ROS) generation. Each of these could also contribute to cerebral edema, which is the primary cause of patient mortality after stroke. In vitro brain slices are widely used to study ischemia.

Glutamate-dependent inhibition of dopamine release in striatum is mediated by a new diffusible messenger, H2O2.

How glutamate regulates dopamine (DA) release in striatum has been a controversial issue. Here, we resolve this by showing that glutamate, acting at AMPA receptors, inhibits DA release by a nonclassic mechanism mediated by hydrogen peroxide (H(2)O(2)). Moreover, we show that GABA(A)-receptor activation opposes this process, thereby enhancing DA release.

NMDA receptor activation mediates hydrogen peroxide-induced pathophysiology in rat hippocampal slices.

Endogenous reactive oxygen species (ROS) can act as modulators of neuronal activity, including synaptic transmission. Inherent in this process, however, is the potential for oxidative damage if the balance between ROS production and regulation becomes disrupted. Here we report that inhibition of synaptic transmission in rat hippocampal slices by H2O2 can be followed by electrical hyperexcitability when transmission returns during H2O2 washout.

Modulation of somatodendritic dopamine release by endogenous H(2)O(2): susceptibility in substantia nigra but resistance in VTA.

We showed previously that dopamine (DA) release in dorsal striatum is inhibited by endogenously generated hydrogen peroxide (H(2)O(2)). Here, we examined whether endogenous H(2)O(2) can also modulate somatodendritic DA release in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), with companion measurements in DA terminal regions. Evoked DA release was monitored in brain slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry.