Activated autologous macrophage implantation in a large-animal model of spinal cord injury.

OBJECT: Axonal regeneration may be hindered following spinal cord injury (SCI) by a limited immune response and insufficient macrophage recruitment. This limitation has been partially surmounted in small-mammal models of SCI by implanting activated autologous macrophages (AAMs). The authors sought to replicate these results in a canine model of partial SCI. METHODS: Six dogs underwent left T-13 spinal cord hemisection. The AAMs were implanted at both ends of the lesion in 4 dogs, and 2 other dogs received sham implantations of cell media. Cortical motor evoked potentials (MEPs) were used to assess electrophysiological recovery. Functional motor recovery was assessed with a modified Tarlov Scale. After 9 months, animals were injected with wheat germ agglutinin-horseradish peroxidase at L-2 and killed for histological assessment. RESULTS: Three of the 4 dogs that received AAM implants and 1 of the 2 negative control dogs showed clear recovery of MEP response. Behavioral assessment showed no difference in motor function between the AAM-treated and control groups. Histological investigation with an axonal retrograde tracer showed neither local fiber crossing nor significant uptake in the contralateral red nucleus in both implanted and negative control groups. CONCLUSIONS: In a large-animal model of partial SCI treated with implanted AAMs, the authors saw no morphological or histological evidence of axonal regeneration. Although they observed partial electrophysiological and functional motor recovery in all dogs, this recovery was not enhanced in animals treated with implanted AAMs. Furthermore, there was no morphological or histological evidence of axonal regeneration in animals with implants that accounted for the observed recovery. The explanation for this finding is probably multifactorial, but the authors believe that the AAM implantation does not produce axonal regeneration, and therefore is a technology that requires further investigation before it can be clinically relied on to ameliorate SCI.

Role of alpha7-nicotinic acetylcholine receptors in tetanic stimulation-induced gamma oscillations in rat hippocampal slices.

Hippocampal gamma oscillations, as a form of neuronal network synchronization, are speculated to be associated with learning, memory and attention. Nicotinic acetylcholine receptor alpha7 subtypes (alpha7-nAChRs) are highly expressed in hippocampal neurons and play important roles in modulating neuronal function, synaptic plasticity, learning and memory. However, little is known about the role of alpha7-nAChRs in hippocampal gamma oscillations. Here, we examined the effects of selective alpha7- and non-alpha7-nAChR antagonists on tetanic gamma oscillations in rat hippocampal slices. We found that brief tetanic stimulation-induced gamma oscillations (30-80 Hz) and pharmacological blockade of alpha7-nAChRs using the relatively selective alpha7-nAChR antagonists, methyllycaconitine (10 or 100 nM) or alpha-bungarotoxin (10 nM), significantly reduced the frequency spectrum power, the number of spikes, and burst duration of evoked gamma oscillations. Neither mecamylamine nor dihydro-beta-erythroidine, which are selective antagonists of non-alpha7-nAChRs, demonstrated significant effects on tetanic gamma oscillations. Nicotine exposure promotes hippocampal gamma oscillations in a methyllycaconitine-sensitive manner. It is concluded that alpha7-nAChRs in hippocampal slices play important roles in regulation of gamma oscillations, thus potentially helping to explain roles of nAChRs in cognitive functions such as learning, memory and attention.

Lumbar disc herniation: microsurgical approach.

Lumbar microdiscectomy IS an effective and time-tested neurosurgical procedure. Appropriate patient selection is as important as surgical technique in ensuring good outcome. As with any operation, mastery of the relevant anatomy is paramount. We offer the following illustrations to help surgeons appreciate this anatomy: specifically, the relationship between the interspace, the nerve root, and the pedicle as seen during a microdiscectomy.

Cerebral revascularization performed using posterior inferior cerebellar artery-posterior inferior cerebellar artery bypass. Report of four cases and literature review.

Cerebral revascularization is often required for the surgical treatment of complex intracranial aneurysms. In certain anatomical locations, vascular anatomy and redundancy make in situ bypass possible. The authors present four patients who underwent revascularization performed using the rarely reported posterior inferior cerebellar artery (PICA)-PICA in situ bypass after their aneurysms had been trapped. At Barrow Neurological Institute, between 1991 and the present, four male patients underwent PICA-PICA by-passes to treat aneurysms involving the vertebral artery, the PICA, or both. The mean age of these patients was 34 years (range 5-49 years). Follow-up studies revealed patent bypasses and no evidence of infarction. Patient outcomes were excellent or good. Multiple surgical techniques have been described for revascularization of at-risk cerebral territories. Often, the blood supply must be derived from extracranial sources through a mobilized pedicle or interposited graft. Certain anatomical locations such as the vertebrobasilar junction, the anterior circle of Willis, and the middle cerebral artery bifurcation are amenable to in situ bypass because there is vessel redundancy or proximity to the contralateral analogous vessel. The advantages of an in situ bypass include one suture line, a short bypass distance, and a close match with the caliber of the recipient graft. Although technically challenging, this technique can be successful and should be considered for appropriate candidates.

Cooling abolishes neuronal network synchronization in rat hippocampal slices.

PURPOSE: We sought to determine whether cooling brain tissue from 34 to 21 degrees C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission. METHODS: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450-500 microm) from Sprague-Dawley male rats, maintained in an air-fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34 degrees C, reduced to 21 degrees C within 20 min. RESULTS: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a gamma-aminobutyric acid (GABA)A-receptor antagonist. Cooling from 34 to 21 degrees C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse-evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner. CONCLUSIONS: Tetany-induced neuronal network synchronization by GABAA-sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity.