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 several molecular pathways that 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 responses and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4h, 8h, 24h and 48h) after 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 4h in the ventral mesencephalon and neuronal death become significantly from 48h. In the striatum, they were significantly increased from 48h after the MPTP administration compared with the control mice. Moreover, p-ERK levels decrease while phospho-p38 expression increases specifically in the striatum from 48h 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.
Background
Occult spinal dysraphism (OSD) encompasses various conditions. A dermal sinus tract (DST) consists of a duct communicating to the skin with deep structures that carries an important risk ...of infection. A different lesion consisting of a translucent skin opening and a fibrous tract that lacks a lumen can also be found in OSD. We termed this lesion
pseudo-dermal sinus
tract.
Patients and methods
We reviewed clinical features of 20 patients with spinal skin orifices. The patients were classified into two categories: group 1 comprised children with true DST and group 2 included patients with skin dimples resembling a DST.
Aims
The aim of this study was to analyze differential features of patients in these two groups as they behaved dissimilarly in regard to clinical significance and outcomes, especially those concerning infectious risk.
Results
Children of group 1 (
n
= 8) presented with tiny skin orifices and with superficial or deep infection. In contrast, group 2 (
n
= 12) mostly manifested with neurological symptoms. No patient in group 2 developed an infection preoperatively. In both groups, magnetic resonance showed tracts that ended in different structures. Histopathology of the lesions were dissimilar, those of group 1 being hollow tubular structures lined by epithelium while those of group 2 being solid tracts of fibrous connective tissue.
Conclusions
DST constitutes a clinicopathological diagnosis. Although sharing some common cutaneous and neuroimaging findings, both groups behaved differently. Patients of group 1 tended to show up with infection requiring urgent surgery. Patients of group 2 often presented with neurological manifestations and skin lesions, but needed no immediate operation.
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.
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.
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.
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.
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.
Highlights • It is a phase I clinical trial on amyotrophic lateral sclerosis that provides research in the field of security beyond the parameters of spirometry or usual scales. • If the patients ...diagnosed with ALS, spinal onset, and duration of disease <36 months have FVC > 50% of predicted, and sleep time oxygen saturation below 90% (T90) ≤2% during 6 months, it is likely that they have stability in breathing pattern 12 months after. • If the patients diagnosed with ALS, spinal onset, and duration of disease <36 months have FVC > 50% of predicted, and sleep time oxygen saturation below 90% (T90) ≤2% during 6 months, it is likely that they have REM sleep preserved 12 months after. • The spinal injection of of autologous bone marrow mononuclear cells in patients with amyotrophic lateral sclerosis is safe and it is possible in ALS patients without worsening the disease.
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.
Abstract 4393
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterised by loss of motoneurons (mns), and it has no cure. Cell therapy has neurotrophic effects in animal ...models and has been proposed as a disease-modifying treatment. Our aim was twofold: firstly, to assess the safety of intraspinal infusion of bone marrow mononuclear cells (BMNC) and, ultimately, to look for histopathological signs of cellular neurotrophism.
We conducted an open single arm phase I trial. After six months observation, autologous BMNC 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) and ALS-FRS, MRC and Norris scales were assessed six and three months prior to the transplant and quarterly afterwards for one 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 non-severe events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were CTCAE 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 1058 postransplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of montoneurons in the treated compared to the untreated segments (4.2+/−0.8 mns/section and 0.9+/−0.3 mns/section, 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 of their neurotrophic activity.
No relevant conflicts of interest to declare.
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