Neurology International最新文献

Headache is a common disorder with high prevalence [...].

Glucocorticoids are used during glioblastoma treatment to prevent the cerebral edema effect surrounding normal brain tissue. The aim of our study was to investigate the long-term effects of multiple administrations of glucocorticoids onto the glycosylated components (proteoglycans and glycosaminoglycans) of normal brain extracellular matrix and the glucocorticoid receptor (GR, Nr3c1) in an experimental model in vivo. Two-month-old male C57Bl/6 mice (n = 90) were injected intraperitoneally with various doses of dexamethasone (DXM) (1; 2.5 mg/kg) for 10 days. The mRNA levels of the GR, proteoglycans core proteins, and heparan sulfate metabolism-involved genes were determined at the 15th, 30th, 60th, and 90th days by a real-time RT-PCR. The glycosaminoglycans content was studied using dot blot and staining with Alcian blue. A DXM treatment increased total GAG content (2-fold), whereas the content of highly sulfated glycosaminoglycans decreased (1.5-2-fold). The mRNA level of the heparan sulfate metabolism-involved gene Hs3St2 increased 5-fold, the mRNA level of Hs6St2 increased6-7-fold, and the mRNA level of proteoglycan aggrecan increased 2-fold. A correlation analysis revealed an association between the mRNA level of the GR and the mRNA level of 8 of the 14 proteoglycans-coding and 4 of the 13 heparan sulfate metabolism-involved genes supporting GR involvement in the DXM regulation of the expression of these genes. In summary, multiple DXM administrations led to an increase in the total GAG content and reorganized the brain extracellular matrix in terms of its glycosylation pattern.

The relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) and phytocannabinoids/endocannabinoids (pCBs/eCBs) has been investigated in a variety of models of peripheral illnesses, with little clarification on their interaction within the central nervous system (CNS). In this context, evidence suggests that the Nrf2-pCBs/eCBS interaction is relevant in modulating peroxidation processes and the antioxidant system. Nrf2, one of the regulators of cellular redox homeostasis, appears to have a protective role toward damaging insults to neurons and glia by enhancing those genes involved in the regulation of homeostatic processes. Specifically in microglia and macroglia cells, Nrf2 can be activated, and its signaling pathway modulated, by both pCBs and eCBs. However, the precise effects of pCBs and eCBs on the Nrf2 signaling pathway are not completely elucidated yet, making their potential clinical employment still not fully understood.

In Alzheimer's disease (AD) pathology, the accumulation of amyloid-beta (Aβ), a main component of senile plaques, activates glial cells and causes neuroinflammation. Excessive neuroinflammation results in neuronal dropouts and finally produces the symptoms of AD. Recent studies suggest that disorder in sphingosine-1-phosphate (S1P) metabolism, especially the decreased expression of sphingosine kinase (SK)1, followed by the reduction in the amount of S1P, can be a promotive factor in AD onset. Thus, we explored the possibility that dysregulated S1P metabolism affects AD through the altered function in glial cells. We evaluated the effect of PF-543, a pharmacological inhibitor of SK1, on the inflammatory responses by lipopolysaccharide (LPS)-activated glial cells, microglia, and astrocytes. The treatment with PF-543 decreased the intracellular S1P content in glial cells. The PF-543 treatment enhanced the nitric oxide (NO) production in the LPS-treated neuron/glia mixed culture. Furthermore, we found that the augmented production of NO and reactive oxygen species (ROS) in the PF-543-treated astrocytes affected the microglial inflammatory responses through humoral factors in the experiment using an astrocyte-conditioned medium. The PF-543 treatment also decreased the microglial Aβ uptake and increased the number of injured neurons in the Aβ-treated neuron/glia mixed culture. These results suggest that a decrease in the glial S1P content can exacerbate neuroinflammation and neurodegeneration through altered glial cell functions.

The pathology of idiopathic intracranial hypertension (IIH), a disease characterized by papillary edema and increased intracranial pressure (IICP), is not yet understood; this disease significantly affects quality of life due to symptoms including vision loss, headache, and pulsatile tinnitus. By contrast, superficial siderosis (SS), a disorder in which hemosiderin is deposited on the surface of the cerebral cortex and cerebellum, potentially causes cerebellar ataxia or hearing loss. So far, no cases of IIH with infratentorial and supratentorial cortical SS have been reported. Herein, we report a case of a 31-year-old woman with obesity who developed this condition. The patient suddenly developed headache and dizziness, had difficulty walking, and subsequently became aware of diplopia. Fundus examination revealed bilateral optic nerve congestive papillae and right eye abducens disturbance. Head magnetic resonance imaging (MRI) showed prominent SS on the cerebellar surface and cerebral cortex. Lumbar puncture revealed IICP of 32 cmH₂O, consistent with the diagnostic criteria for IIH, and treatment with oral acetazolamide was started; subsequently, the intracranial pressure decreased to 20 cmH₂O. Her abduction disorder disappeared, and the swelling of the optic papilla improved. She was now able return to her life as a teacher without any sequelae. SS is caused by persistent slight hemorrhage into the subarachnoid space. In this case, both infratentorial and supratentorial cortical superficial SS was observed. Although cases of IIH complicated by SS are rare, it should be kept in mind that a causal relationship between IIH and SS was inferred from our case. Our findings also suggest that cerebrospinal fluid dynamic analysis using MRI is effective in diagnosing IIH and in determining the efficacy of treatment.

Diffuse axonal injury (DAI) following sudden acceleration and deceleration can lead to cognitive function decline. Various treatments have been proposed. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique, is a potential treatment for enhancing neuroplasticity in cases of brain injury. The therapeutic efficacy of rTMS on cognitive function remains unconfirmed. This study investigated the effects of rTMS and the underlying molecular biomechanisms using a rat model of DAI. Sprague-Dawley rats (n = 18) were randomly divided into two groups: one receiving rTMS after DAI and the other without brain stimulation. All rats were subjected to sudden acceleration and deceleration using a DAI modeling machine to induce damage. MRI was performed to confirm the DAI lesion. The experimental group received rTMS at a frequency of 1 Hz over the frontal cortex for 10 min daily for five days. To assess spatial memory, we conducted the Morris water maze (MWM) test one day post-brain damage and one day after the five-day intervention. A video tracking system recorded the escape latency. After post-MWM tests, all rats were euthanized, and their brain tissues, particularly from the hippocampus, were collected for immunohistochemistry and western blot analyses. The escape latency showed no difference on the MWM test after DAI, but a significant difference was observed after rTMS between the two groups. Immunohistochemistry and western blot analyses indicated increased expression of BDNF, VEGF, and MAP2 in the hippocampal brain tissue of the DAI-T group. In conclusion, rTMS improved cognitive function in the DAI rat model. The increased expression of BDNF, VEGF, and MAP2 in the DAI-T group supports the potential use of rTMS in treating cognitive impairments associated with DAI.

Background: the aim of this study was to investigate the neurophysiological effect of anti-CGRP monoclonal antibodies on central and peripheral levels in migraine patients.

Methods: An observational cohort study in patients with migraine was performed. All subjects underwent Single-Pulse and Paired-Pulse Transcranial Magnetic Stimulation, as well as a Pressure Pain Threshold assessment. The same protocol was repeated three and four months after the first injection of anti-CGRP monoclonal antibodies.

Results: A total of 11 patients with a diagnosis of migraine and 11 healthy controls were enrolled. The main findings of this study are the significant effects of anti-CGRP mAb treatment on the TMS parameters of intracortical inhibition and the rise in the resting motor threshold in our group of patients affected by resistant migraine. The clinical effect of therapy on migraine is associated with the increase in short-interval intracortical inhibition (SICI), resting motor threshold (RMT), and Pressure Pain Threshold (PPT). In all patients, all clinical headache parameters improved significantly 3 months after the first injection of mAbs and the improvement was maintained at the 1-month follow-up. At baseline, migraineurs and HCs had significant differences in all TMS parameters and in PPT, while at follow-up assessment, no differences were observed on RMT, SICI, and PPT between the two groups. After anti-CGRP monoclonal antibody injection, a significant increase in the intracortical inhibition, in the motor threshold, and in the Pressure Pain Threshold in critical head areas was observed in patients with migraine, which was related to significant clinical benefits.

Conclusions: Anti-CGRP monoclonal antibodies improved clinical and neurophysiological outcomes, reflecting a normalization of cortical excitability and peripheral and central sensitization. By directly acting on the thalamus or hypothalamus and indirectly on the trigeminocervical complex, treatment with anti-CGRP monoclonal antibodies may modulate central sensorimotor excitability and peripheral sensitization pain.

Background: In patients with acute ischemic stroke, the standard of care is to perform intra-arterial endovascular thrombectomy in addition to intravenous thrombolysis. In this study, we investigated the different anesthetic techniques chosen for this procedure and clinical outcomes.

Methods: Patients undergoing endovascular procedures were divided into three groups. The first group consisted of patients who received general anesthesia, the second group underwent the procedure under conscious sedation and local anesthesia at the catheter insertion site, and lastly the third group included patients who received only local anesthesia at the catheter insertion site, without sedation.

Results: During the endovascular procedure, we did not notice significant differences in vital parameters, in particular the mean blood pressure (MAP) between patients treated with different types of anesthesia. Also, the duration of the revascularization did not show significant differences between the three groups. The main point is the absence of differences in terms of functional and clinical outcomes, using various scores as reference, such as the National Institutes of Health Stroke Scale (NIHSS) score at 7 days, NIHSS and Modified Rankin Scale (MRS) at time of discharge, and MRS after 3 months. These scores did not show significant differences in groups treated with different types of anesthesia.

Conclusions: The rate of success of the revascularization procedure is almost overlapping between patients treated with conscious sedation and general anesthesia. In addition, we did not notice significant differences between groups in terms of functional and clinical outcomes. Considering the possible usefulness of applying conscious sedation, at OCSAE of Baggiovara, an internal protocol for conscious sedation was introduced to standardize the treatment in patients undergoing endovascular procedures.