Study of the Link Between Neuronal Death, Glial Response, and MAPK Pathway in Old Parkinsonian Mice.

Background: Parkinson's disease (PD) is described as an age-related neurodegenerative disorder. However, the vast majority of research is carried out using experimental models of young animals lacking the implications of the decline processes associated with aging. It has been suggested that several molecular pathways are involved in the perpetuation of the degeneration and the neuroinflammation in PD. Among others, mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets. Methods: To further define how MAPKs expression is related to the glial response and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4, 8, 24, and 48 h) after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) injections to describe the early dynamic changes over time produced by the intoxication. Results: The results revealed that neuronal death increases as glial response increases in the nigrostriatal pathway. It was observed that both processes increase from 4 h in the ventral mesencephalon (VM), and neuronal death becomes significant at 48 h. In the striatum, they were significantly increased from 48 h after the MPTP administration compared with that in the control mice. Moreover, the p-ERK levels decrease, while phospho-p38 expression increases specifically in the striatum at 48 h after MPTP intoxication. Conclusions: The importance of these data lies in the possibility of elucidating the underlying mechanisms of neurodegenerative processes under aging conditions to provide knowledge for the search of solutions that slow down the progression of PD.

Breathing pattern in a phase I clinical trial of intraspinal injection of autologous bone marrow mononuclear cells in patients with amyotrophic lateral sclerosis.

The safety of autologous bone marrow mononuclear cells (ABMNC) intraspinal infusion in amyotrophic lateral sclerosis (ALS) patients was evaluated considering breathing and sleep patterns. Patients between 20 and 65 years old were eligible if they had definite ALS, spinal onset, a disease duration between 6 and 36 months, FVC>50%, and a below 90% oxygen saturation (T90) <2% of sleep time. The transplant was performed 6 months after enrollment. ABMNC were infused at thoracic 3-4 level. Eleven patients were included. The REM sleep decreased slightly one year after the cell transplant but not significantly. There were no differences in apnea-hipopnea index, mean oxygen saturation and nadir desaturation evolution. An increase of T90 was observed 180 and 360 days after injection (2.95±1.51% and 4.30±4.10% respectively), although it was not statistically significant. The central drive determined by occlusion pressure (P01) and inspiratory flow showed non-significant differences after one year. Intramedullary injection of ABMNC did not worsen the cortico medullar diaphragmatic pathways.

Retinal aging in the diurnal Chilean rodent (Octodon degus): histological, ultrastructural and neurochemical alterations of the vertical information processing pathway.

The retina is sensitive to age-dependent degeneration. To find suitable animal models to understand and map this process has particular importance. The degu (Octodon degus) is a diurnal rodent with dichromatic color vision. Its retinal structure is similar to that in humans in many respects, therefore, it is well suited to study retinal aging. Histological, cell type-specific and ultrastructural alterations were examined in 6-, 12- and 36-months old degus. The characteristic layers of the retina were present at all ages, but slightly loosened tissue structure could be observed in 36-month-old animals both at light and electron microscopic levels. Elevated Glial fibrillary acidic protein (GFAP) expression was observed in Müller glial cells in aging retinas. The number of rod bipolar cells and the ganglion cells was reduced in the aging specimens, while that of cone bipolar cells remained unchanged. Other age-related differences were detected at ultrastructural level: alteration of the retinal pigment epithelium and degenerated photoreceptor cells were evident. Ribbon synapses were sparse and often differed in morphology from those in the young animals. These results support our hypothesis that (i) the rod pathway seems to be more sensitive than the cone pathway to age-related cell loss; (ii) structural changes in the basement membrane of pigment epithelial cells can be one of the early signs of degenerative processes; (iii) the loss of synaptic proteins especially from those of the ribbon synapses are characteristic; and (iv) the degu retina may be a suitable model for studying retinal aging.

Comparison of the Effects of Propofol and Sevoflurane Combined With Remifentanil on Transcranial Electric Motor-evoked and Somatosensory-evoked Potential Monitoring During Brainstem Surgery.

BACKGROUND: We compared the effect of propofol and sevoflurane combined with remifentanil under comparable bispectral index (BIS) levels on transcranial electric motor-evoked potentials (TceMEPs) and somatosensory-evoked potentials (SSEPs) during brainstem surgery. MATERIALS AND METHODS: A total of 40 consecutive patients (20 per group) undergoing brainstem surgery were randomly assigned to 2 groups receiving either 0.5 MAC sevoflurane or propofol at an effect-site concentration of 2.5 µg/mL for maintenance of anesthesia. Remifentanil was administered to both groups at a rate of 0.25 to 0.35 µg/kg/min along with cisatracurium (0.03 to 0.04 mg/kg/h). TceMEP recordings were carried out in the abductor pollicis brevis, abductor hallucis, and tibialis anterior muscles, whereas cortical SSEPs were measured with posterior tibial nerve stimulation. Amplitudes and latencies of TceMEPs and SSEPs were recorded at 1, 2, 3, and 4 hours after the induction of anesthesia. RESULTS: BIS values remained in the 45 to 60 range. Amplitudes of TceMEPs were significantly higher in the propofol group than those in the sevoflurane group (P<0.05, at all study time points in abductor pollicis brevis and abductor hallucis muscles and only 4 h after anesthetic induction for tibialis anterior muscle), whereas latencies were shorter in the propofol group than those in the sevoflurane group (P<0.05). No differences were observed in latency and amplitude while recording SSEPs between the 2 anesthetic techniques. None of the patients had TceMEPs and SSEPs amplitude or latency changes, exceeding our set limit. CONCLUSIONS: Both sevoflurane and propofol at low dosages combined with remifentanil under comparable BIS values and partial muscle relaxation can be used when monitoring of TceMEPs and SSEPs is required for brainstem surgery.

Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study.

The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity.

Cervical spinal cord infarction after posterior fossa surgery: a case-based update.

BACKGROUND: Several positions are currently utilized for operating patients with posterior fossa lesions. Each individual position has its own risks and benefits, and none has demonstrated its superiority. A dreaded, and probably underreported, complication of these procedures is cervical cord infarction with quadriplegia. DISCUSSION: We reviewed eight previous reported instances of this devastating complication aimed at ascertaining its pathogenesis to suggest preventive strategies. Several hypotheses have been put forward to explain the occurrence of this complication. Some factors involved in the production of cervical cord infarction include patient's position (seated or prone), hyperflexion of the neck, excessive spinal cord traction, canal stenosis, and systemic arterial hypotension. We hypothesize that spinal cord infarction in our patient might have resulted from compromised blood supply to the midcervical cord caused by tumor infiltration of the cervical leptomeninges in addition to a brief episode of arterial hypotension during venous air embolism. CASE REPORT: We treated an 8-year-old girl who developed quadriplegia after surgery for a fourth ventricular ependymoma. Postoperative magnetic resonance imaging demonstrated cervical cord infarction. Evoked potentials confirmed the diagnosis. CONCLUSIONS: With this report, we want to draw the attention of neurosurgeons to the possibility of the occurrence of this dreadful complication during posterior fossa procedures. Retrospectively, the only measures that might have helped to avoid this complication in our patient would have been using the prone position and intraoperative monitoring of evoked potentials.

Partial conduction blocks in N-hexane neuropathy.

Nerve conduction blocks, defined by a significant reduction in amplitude or area of the compound muscle action potential at proximal compared with distal sites of stimulation, have been described in glue-sniffers and in workers with industrial exposure at an early stage of n-hexane neuropathy. The frequency with which this focal conduction anomaly appears is described and discussed in the case of a very homogeneous group of 10 young workers diagnosed with n-hexane polyneuropathy. Partial conduction blocks occurred in only two workers and may have been related to the intensity and duration of toxic exposure.