Membrane resonance in bursting pacemaker neurons of an oscillatory network is correlated with network frequency.

Network oscillations typically span a limited range of frequency. In pacemaker-driven networks, including many central pattern generators (CPGs), this frequency range is determined by the properties of bursting pacemaker neurons and their synaptic connections; thus, factors that affect the burst frequency of pacemaker neurons should play a role in determining the network frequency. We examine the role of membrane resonance of pacemaker neurons on the network frequency in the crab pyloric CPG. The pyloric oscillations (frequency of approximately 1 Hz) are generated by a group of pacemaker neurons: the anterior burster (AB) and the pyloric dilator (PD). We examine the impedance profiles of the AB and PD neurons in response to sinusoidal current injections with varying frequency and find that both neuron types exhibit membrane resonance, i.e., demonstrate maximal impedance at a given preferred frequency. The membrane resonance frequencies of the AB and PD neurons fall within the range of the pyloric network oscillation frequency. Experiments with pharmacological blockers and computational modeling show that both calcium currents I(Ca) and the hyperpolarization-activated inward current I(h) are important in producing the membrane resonance in these neurons. We then demonstrate that both the membrane resonance frequency of the PD neuron and its suprathreshold bursting frequency can be shifted in the same direction by either direct current injection or by using the dynamic-clamp technique to inject artificial conductances for I(h) or I(Ca). Together, these results suggest that membrane resonance of pacemaker neurons can be strongly correlated with the CPG oscillation frequency.

Very mild stroke patients benefit from intravenous tissue plasminogen activator without increase of intracranial hemorrhage.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (IV rt-PA) is an effective medication currently used to treat acute ischemic stroke within three hours of symptom onset in patients with an identifiable clinical deficit measured using the National Institute of Health Stroke Scale (NIHSS). METHODS: We compared the outcomes of 27 identified patients with an NIHSS of 6 or less who received IV rt-PA for acute ischemic stroke treatment within three hours of symptom onset in our center with 24 historic controls from the nationally available National Institute of Neurological Disorders and Stroke (NINDS) study database. RESULTS: The mean initial NIHSS was not significantly different in patients and control groups (mean +/- SD: 4.52 +/- 1.25 and 4.71 +/- 1.4) (P = 0.45). The mean modified Rankin score (mRS) at the time of discharge in patients and control group were 0.78 +/- 1.19 and 1.75 +/- 1.75, respectively. The mRS at discharge demonstrated a statistically significant (P < 0.03) improved clinical outcome for IV rt-PA treated group. The rate of intracranial hemorrhage (ICH) in the IV rt-PA group and control group was not significantly different (P = 1, odds ratio: 0.88, CI: 0.05-14.09). CONCLUSION: This retrospective study demonstrates that administering intravenous rt-PA to patients with a very mild stroke (NIHSS of 6 or less) can lead to improved clinical outcome when compared to patients with similar NIHSS who have not received similar treatment.

Evidence for Dietary Agmatine Sulfate Effectiveness in Neuropathies Associated with Painful Small Fiber Neuropathy. A Pilot Open-Label Consecutive Case Series Study.

Peripheral neuropathies associated with painful small fiber neuropathy (SFN) are complex conditions, resistant to treatment with conventional medications. Previous clinical studies strongly support the use of dietary agmatine as a safe and effective treatment for neuropathic pain. Based on this evidence, we conducted an open-label consecutive case series study to evaluate the effectiveness of agmatine in neuropathies associated with painful SFN (Study Registry: ClinicalTrials.gov, System Identifier: NCT01524666). Participants diagnosed with painful SFN and autonomic dysfunctions were treated with 2.67 g/day agmatine sulfate (AgmaSet® capsules containing G-Agmatine® brand of agmatine sulfate) for a period of 2 months. Before the beginning (baseline) and at the end of the treatment period, participants answered the established 12-item neuropathic pain questionnaire specifically developed to distinguish symptoms associated with neuropathy and to quantify their severity. Secondary outcomes included other treatment options and a safety assessment. Twelve patients were recruited, and 11 patients-8 diagnosed with diabetic neuropathy, two with idiopathic neuropathy and one with inflammatory neuropathy-completed the study. All patients showed improvement in neuropathic pain to a varied extent. The average decrease in pain intensity was 26.0 rating points, corresponding to a 46.4% reduction in overall pain (p < 0.00001). The results suggest that dietary agmatine sulfate has a significant effect in reducing neuropathic pain intensity associated with painful SFN resistant to treatment with conventional neuropathic pain medications. Larger randomized placebo-controlled studies are expected to establish agmatine sulfate as a preferred treatment.

Combining synaptic and cellular resonance in a feed-forward neuronal network.

We derive a mathematical theory to explain the subthreshold resonance response of a neuron to synaptic input. The theory shows how a neuron combines information from its intrinsic resonant properties with those of the synapse to determine the neuron's generalized resonance response. Our results show that the maximal response of a postsynaptic neuron can lie between the preferred intrinsic frequency of the neuron and the synaptic resonance frequency. We compare our theoretical results to parallel findings on experiments of the crab pyloric central pattern generator.

Recanalization following various endovascular modalities for treatment of anterior circulation acute ischemic strokes.

Currently several endovascular modalities and devices are available for use in acute ischemic stroke setting. Limited data exist regarding the relative efficacy of these different options when used individually or in combination. The primary objective of this study was to retrospectively compare the recanalization rates of various endovascular options when used for the treatment of acute ischemic stroke in the anterior cerebral circulation. We retrospectively reviewed 132 consecutive patients treated endovascularly at our center for acute ischemic stroke in the anterior cerebral circulation. Recanalization was defined as mTIMI of ≥ 2 while complete recanalization was defined as mTIMI of 4. Statistical analysis was performed to determine the modality or combination of modalities associated with best recanalization rate. Recanalization was achieved in 74% of patients while complete recanalization was achieved in 39% of patients. No individual endovascular therapy was significantly different from others in achieving recanalization. Where a multimodality approach was used, combination of angioplasty with intra- or extracranial stent placement was significantly (p=0.05) associated with recanalization. On regression analysis, combination of intra-arterial tPA with a mechanical modality (p=0.09) was significantly associated with recanalization while combination of intravenous tPA with intracranial stent placement (p=0.06) was significantly associated with complete recanalization. Combination of pharmacological and mechanical modalities in the setting of multimodal therapy is associated with increased likelihood of successful recanalization in patients with acute ischemic stroke in the anterior cerebral circulation. Stent placement in acute stroke setting is promising and needs further exploration. Further prospective studies are needed.