Effect of neonatal neuronal intensive care unit on neonatal encephalopathy

Prophylaxis of brain injury in newborns has been a main concern since the first neonatal neuronal intensive care unit (NNICU) was established in the world in 2008. The aim of this study was to outline and evaluate the unit’s development by analyzing the demographics of the patients, the services delivered, the short-term outcomes before and after the establishment of NNICU. During the two investigation periods, 384 newborns were diagnosed or suspected as “neonatal encephalopathy”, among which 185 patients admitted to NNICU between 2011.03.01 and 2012.09.30 before the establishment of NNICU were enrolled in the pre-NNICU group, another 199 neonates hospitalized during 2018.03.01 to 2019.09.30 were included in the post-NNICU group. Patients in the post-NNICU group were more likely to have seizures (P = 0.001), incomplete or absent primitive reflexes (P = 0.002), therapeutic hypothermia (P<0.001) and liquid control (P<0.001) in acute phase. Meanwhile, amplitude-integrated electro encephalogram (aEEG) monitoring (P<0.001) and cranial ultrasound (P<0.001) were more often used in NNICU. Both of the follow-up rate in brain MRI and the assessment of neurodevelopment at 3 months were higher in the post-NNICU group (P<0.001). In conclusion, the NNICU focused on the neonatal neurocritical care for the babies susceptible to NE with the guidance of evidence-based medicine, the establishment of NNICU is gradually improving and standardizing the neuroprotective therapy and clinical follow-up to improve neurodevelopmental prognosis of the NE patients in CHCMU.

Review: Neuroprotective effect of herbal plant extracts against Parkinson's disease

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons and the exist of alpha-synuclein aggregates in the substantia nigra pars compacta (SNpc). Among the various types of neuroprotective therapy, natural products are potential therapeutic agents for PD. Objective: The aim of this study is to describe the neuroprotective effect of herbal plant extracts against Parkinson's Disease (PD). Method: The search strategy was carried out on electronic databases, namely Google Scholar, ScienceDirect, and PubMed. There are 111 scientific journals that have been filtered into 20 scientific journals which are international journals published in the last 5 years (2015-2020). The keywords used include Parkinson's Disease, Neuroprotective Effects, Neuroprotection, Plant Extracts, Natural Products and Parkinson's Disease Model. Results: Several experimental studies have shown the neuroprotective ability of various plant extracts to protect against neurotoxicity, through several neuroprotective pathways including antioxidant activity, anti-inflammatory activity, and antiapoptotic activity. Conclusion: Herbal plant extracts have been shown to have strong neuroprotective effects, making them as potential drug candidates for prevention or treatment of Parkinson's Disease (PD). There are Mucuna pruriens, Centella asiatica, Camellia sinensis, Ginkgo biloba, and Uncaria rhynchophylla. Keywords: Parkinson's Disease (PD), neuroprotective, extract.

Neurologic Complications in Adult and Pediatric Patients with SARS-CoV-2 Infection

SARS-CoV-2 has an impact on the nervous system as a result of pathological cellular and molecular events at the level of vascular and neural tissue. Severe neurologic manifestations including stroke, ataxia, seizure, and depressed level of consciousness are prevalent in patients with SARS-CoV-2 infection. Although the mechanism is still unclear, SARS-CoV-2 has been associated with the pathogenesis of intravascular coagulation and angiotensin-converting enzyme-I, both exacerbating systemic inflammation and contributing to hypercoagulation or blood–brain barrier leakage, resulting in ischemic or hemorrhagic stroke. On the other hand, the SARS-CoV-2 spike protein in neural tissue and within the cerebrospinal fluid may induce neural dysfunction, resulting in neuroinflammation, which is exacerbated by peripheral and neural hypercytokinemia that can lead to neuronal damage and subsequent neuroinflammation. A deeper understanding of the fundamental biological mechanisms of neurologic manifestations in SARS-CoV-2 infection can pave the way to identifying a single biomarker or network of biomarkers to help target neuroprotective therapy in patients at risk for developing neurological complications.

The Current Status of Neuroprotection in Congenital Heart Disease

Neurological deficits are a serious and common sequelae of congenital heart disease (CHD). While their underlying mechanisms have not been fully characterized, their manifestations are well-known and understood to persist through adulthood. Development of therapies to address or prevent these deficits are critical to attenuate future morbidity and improve quality of life. In this review, we aim to summarize the current status of neuroprotective therapy in CHD. Through an exploration of present research in the pre-operative, intra-operative, and post-operative phases of patient management, we will describe existing clinical and bench efforts as well as current endeavors underway within this research area.

Impact of neuroprotective therapy on cognition and oxidative stress in the early stages of Parkinson’s disease

The aim of this study was to investigate the clinical and biochemical efficiency of citicoline in cognitive improvement and changes of glutathione peroxidase (GPx) blood plasma levels in patients at early stages of Parkinson’s disease (PD). Materials and methods. We recruited 42 patients at I–II Hoehn and Yahr PD stages and 20 controls. The Montreal Cognitive Assessment test (MoCA) was used to assess several cognitive domains in PD patients (before citicoline treatment, after intravenous therapy and after pills therapy) and controls (once). Plasma was collected once in controls and twice in PD patients (on the first and the last days of observation). Citicoline was administrated to 23 of 42 PD patients in addition to basic antiparkinsonian therapy intravenously during 10 days and with pills during next 30 days. The rest 19 of 42 PD patients had been taking basic antiparkinsonian treatment only (comparison group). Results. We observed significant improvement of MoCA scores in PD patients with citicoline course (PD-Cs) in each check day. But in spite of such an improvement in PD patients, who were left on the basic antiparkinsonian treatment (PD-Bs), on the 10th day of observation, patients of this group did not keep it to the last day of the research (P < 0.001). After the treatment the GPx level in plasma of PD-Cs was significantly higher than in PD-Bs (P < 0.001). Furthermore, the activity of GPx plasma level after citicoline course was significantly higher than before additional neuroprotective therapy, which wasn’t observed in PD patients on basic treatment only. Conclusion. The cognition of PD patients (according to MoCA scores) at the early stages of the disease was significantly improved after citicoline treatment. Citicoline treatment had significant positive influence on the increasing antioxidant GPx plasma activity in PD patients at the early stages of the disease.

Neuroprotective therapy for glaucoma (literature review)

This literature review presents data on neuroprotection in glaucoma. In neuroprotective therapy, it is desirable to use a comprehensive treatment that includes drugs of various pharmacological groups acting on different pathogenetic links of glaucoma optical neuropathy. One of the most promising areas of neuroprotection is the simultaneous combined effect of various physical factors (with mutual potency of their therapeutic action) and drug therapy, which increases the neuroprotective effect. However, treatment should be performed against the background of absolutely normalized intraocular pressure. Key words: glaucoma, glaucoma optical neuropathy, neuroprotection, drug therapy, normalized intraocular pressure.

Efficacy of rituximab in autism spectrum disorders associated with hereditary folate malabsorption with signs of antineuronal autoimmunity

Background. One of the key advances in psychiatry is an elucidation of the association of hereditary folate malabsorption (HFM) with autistic spectrum disorders (ASD), the evidence for which is based on the results of 5 meta-analyses of randomized controlled trials. It is shown that in such cases the antineuronal autoimmune reaction is an important mechanism of encephalopathy formation. The purpose of the study was to investigate the efficacy of rituximab in children with HFM-associated ASD who showed serological signs of antineuronal autoimmunity to expand the current arsenal of neuroprotective therapy in immunodependent encephalopathy in such cases. Materials and methods. Medical data of 138 children aged 3 to 8 years with HFM and ASD (97 boys and 41 girls) were analyzed. Parents of 62 of 81 patients with signs of antineuronal autoimmunity agreed to rituximab immunotherapy at a dose of 375 mg/m2 of body surface area per month for 3–9 months (study group, SG). Relatives of the other 19 patients with a similar distribution of antineuronal autoantibodies refused treatment (control group, CG). The dynamics of the mental state of children during immunotherapy was assessed by the ABC scale. For statistical analysis, we calculated the parametric Student’s t-test with the confidence probability p and the non-parametric criterion — the number of signs Z by U.V. Urbach, as well as the odds ratio (OR) and 95% confidence interval (95% CI). Results. Rituximab treatment resulted in a progressive decrease in serum antineuronal autoantibodies concentration in patients with ASD associated with HFM, with a more pronounced effect in the production of autoantibodies to neuronal potassium channels compared to autoantibodies to the GADA with complete elimination of the seropositivity after a 9-month course of immunotherapy in 92 % of cases. The phenomenon of rituximab-induced elimination of serum antineuronal autoantibodies is associated with the effect of neuroprotection, which was confirmed by the normalization of previously elevated serum concentrations of laboratory biomarkers of NSE cerebral damage (OR = 17.875; 95% CI = 4.738–67.436 at Ab to GADA and 41.800; 7.257–240.778 at Ab to potassium channels) and S-100 protein (9.750; 2.707–35.113 and 18.333; 3.462–97.083, respectively). In parallel, there was a progressive improvement in all indicators of the mental status of children with ASD on the ABC scale with a latency period of about 2 months (p < 0.05: Z < Z0.05). Conclusions. Immunotherapy with rituximab by eliminating the serological signs of antineuronal autoimmunity realizes the effect of neuroprotection, reducing the severity of all major clinical signs of ASD in children with HFM.

Immunization with neural-derived peptides as a neuroprotective therapy for spinal cord injury

Spinal cord injury (SCI) induces several destructive events that develop immediately after the primary insult. These phenomena increase tissue damage; that is why, numerous therapeutic approaches are studied in order to neutralize these destructive mechanisms. In line with this, several studies indicate that after injury, neural tissue could be protected by an adaptive immune response directed against self-antigens. Immunization with neural-derived peptides (INDP) reduces secondary degeneration of neurons after spinal cord insult and promotes a significant motor recovery. The combination of antioxidants or other immunomodulatory peptides after SCI can improve the protective effect induced by INDP. INDP in acute SCI is a promising strategy, so further studies should be addressed to be able to formulate the best strategy.

Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease, with no present cure. The progressive loss of MNs is the hallmark of ALS. We have previously shown the therapeutic effects of the phosphatase and tensin homolog (PTEN) inhibitor, potassium bisperoxo (picolinato) vanadium (bpV[pic]), in models of neurological injury and demonstrated significant neuroprotective effects on MN survival. However, accumulating evidence suggests PTEN is detrimental for MN survival in ALS. Therefore, we hypothesized that treating the mutant superoxide dismutase 1 G93A (mSOD1G93A) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1G93A motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1G93A mice intraperitoneally daily with 400 μg/kg bpV(pic) from 70 to 90 days of age. Immunolabeled MNs and microglial reactivity were analyzed in lumbar spinal cord tissue, and bpV(pic) treatment significantly ameliorated ventral horn motor neuron loss in mSOD1G93A mice (p = 0.003) while not significantly altering microglial reactivity (p = 0.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation (p = 0.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1G93A and starved them in serum-free medium for 24 h with and without bpV(pic) and downstream inhibitor of Akt signaling, LY294002. In vitro, bpV(pic) improved neuronal viability, and Akt inhibition reversed this protective effect (p < 0.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.

Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma

Ocular repeated air blast injuries occur from low overpressure blast wave exposure, which are often repeated and in quick succession. We have shown that caspase-2 caused the death of retinal ganglion cells (RGC) after blunt ocular trauma. Here, we investigated if caspase-2 also mediates RGC apoptosis in a mouse model of air blast induced indirect traumatic optic neuropathy (b-ITON). C57BL/6 mice were exposed to repeated blasts of overpressure air (3 × 2 × 15 psi) and intravitreal injections of siRNA against caspase-2 (siCASP2) or against a control enhanced green fluorescent protein (siEGFP) at either 5 h after the first 2 × 15 psi (“post-blast”) or 48 h before the first blast exposure (“pre-blast”) and repeated every 7 days. RGC counts were unaffected by the b-ITON or intravitreal injections, despite increased degenerating ON axons, even in siCASP2 “post-blast” injection groups. Degenerating ON axons remained at sham levels after b-ITON and intravitreal siCASP2 “pre-blast” injections, but with less degenerating axons in siCASP2 compared to siEGFP-treated eyes. Intravitreal injections “post-blast” caused greater vitreous inflammation, potentiated by siCASP2, with less in “pre-blast” injected eyes, which was abrogated by siCASP2. We conclude that intravitreal injection timing after ocular trauma induced variable retinal and ON pathology, undermining our candidate neuroprotective therapy, siCASP2.