Is a Neuroprotective Therapy Suitable for Schizophrenia Patients?

Background: Dementia is a common medical disorder in the elderly. Oxidative stress plays a major role in the process of cognitive decline in dementia. Perilla seed oil demonstrates its neuroprotective effects via anti-oxidative mechanisms against dementia. We investigate neuroprotective effects of perilla seed oil as an additional treatment in patients with mild to moderate dementia. </P><P> Method: A double-blind, randomized-control trial (perilla seed oil versus placebo) in patients with mild to moderate dementia was conducted. Perilla seed oil or placebo was added on with standard treatment for six months. Cognitive function was compared at nine months after enrollment. </P><P> Result: 182 patients, with 94 in the experimental group and 88 in the placebo group, were able to complete the study. Cognitive function is not significantly different compared between groups. However, the total cholesterol and LDL cholesterol were significantly lower in the experimental group. Perilla seed oil had no adverse effect to kidney, liver, blood components or glucose metabolism. Conclusion: Perilla seed oil as additional neuroprotective therapy in patients with mild to moderate dementia does not improve cognitive function. Perilla seed oil significantly reduced total cholesterol and LDL cholesterol. A clinical trial is needed to prove the benefit of cholesterol-lowering effects with perilla seed oil in human.

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

Scientific Reports ◽

10.1038/s41598-021-96107-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chloe N. Thomas ◽

Alexandra Bernardo-Colón ◽

Ella Courtie ◽

Gareth Essex ◽

Tonia S. Rex ◽

...

Keyword(s):

Intravitreal Injection ◽

Fluorescent Protein ◽

Ocular Trauma ◽

Ganglion Cells ◽

Intravitreal Injections ◽

Nerve Degeneration ◽

Injection Timing ◽

Air Blast ◽

Neuroprotective Therapy ◽

Caspase 2

AbstractOcular 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.

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Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis

Brain Sciences ◽

10.3390/brainsci11030325 ◽

2021 ◽

Vol 11 (3) ◽

pp. 325

Author(s):

Fatima M. Shakova ◽

Yuliya I. Kirova ◽

Denis N. Silachev ◽

Galina A. Romanova ◽

Sergey G. Morozov

Keyword(s):

Rat Model ◽

Nuclear Translocation ◽

Peroxisome Proliferator ◽

Protective Effects ◽

Protein Markers ◽

Peroxisome Proliferator Activated Receptor ◽

Pharmacological Agents ◽

Ischemic Brain ◽

Neuroprotective Therapy ◽

Dependent Protein

The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH(4–7) analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex. Mexidol (100 mg/kg) was administered intraperitoneally, and Semax (25 μg/kg) was administered intranasally, for 7 days each. The expression of PGC-1α and PGC-1α-dependent protein markers of mitochondriogenesis, angiogenesis, and synaptogenesis was measured in the penumbra via immunoblotting at Days 1, 3, 7, and 21 after PT. The nuclear content of PGC-1α was measured immunohistochemically. The suppression of PGC-1α expression was observed in the penumbra from 24 h to 21 days following PT and reflected decreases in both the number of neurons and PGC-1α expression in individual neurons. Administration of Mexidol or Semax was associated with preservation of the neuron number and neuronal expression of PGC-1α, stimulation of the nuclear translocation of PGC-1α, and increased contents of protein markers for PGC-1α activation. This study opens new prospects for the pharmacological modulation of PGC-1α in the ischemic brain.

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Neuroprotective Therapy

Current Review of Cerebrovascular Disease ◽

10.1007/978-1-4684-0001-4_18 ◽

2001 ◽

pp. 197-206

Author(s):

Nils Gunnar Wahlgren ◽

Magnus Thorén

Keyword(s):

Neuroprotective Therapy

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

Molecular Brain ◽

10.1186/s13041-021-00867-7 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Junmei Wang ◽

Lydia Tierney ◽

Ranjeet Mann ◽

Thomas Lonsway ◽

Chandler L. Walker

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Lumbar Spinal Cord ◽

Therapeutic Effects ◽

Spinal Cord Tissue ◽

Neuron Loss ◽

Neuroprotective Therapy ◽

Motor Neuron Loss ◽

Lateral Sclerosis

AbstractAmyotrophic 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.

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Potential Neuroprotective Therapy for Glaucoma

Arquivos Brasileiros de Oftalmologia ◽

10.5935/0004-2749.19990040 ◽

1999 ◽

Vol 62 (2) ◽

Author(s):

Michal Schwartz ◽

Eti Yoles ◽

Michael Belkin

Keyword(s):

Neuroprotective Therapy

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Neuroprotective therapy in chronic cerebrovascular diseases

Russian neurological Journal ◽

10.30629/2658-7947-2021-26-4-46-49 ◽

2021 ◽

Vol 26 (4) ◽

pp. 46-49

Author(s):

O. V. Kim ◽

Yo. N. Madzhidova ◽

F. R. Sharipov

Keyword(s):

Mini Mental State Examination ◽

Depression Scale ◽

Neurological Status ◽

Cerebrovascular Diseases ◽

Depression Score ◽

Anxiety And Depression ◽

Basic Therapy ◽

Neuroprotective Therapy ◽

State Examination ◽

Moca Score

Introduction. In chronic cerebrovascular diseases (CVD), neuroprotective medications, the effectiveness of which requires further study, are widely used. The effectiveness of Cytoflavinum in patients with chronic CVD was evaluated.Material and methods. The data of 60 patients (35 women and 25 men) with chronic CVD were analyzed. 30 patients, included in the main group (mean age 61 ± 5.87 years old), in addition to basic therapy (antihypertensive, antithrombotic drugs, statins), received Cytoflavinum according to the following scheme: 1 time a day in the morning intravenously 10.0 ml for 10 days, then 2 tablets 2 times a day for 30 days. 30 patients in the comparison group (mean age 59.8 ± 8.7 years old) received only basic therapy. An analysis of patient complaints, neurological status was carried out. Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS) were used.Results. In the group of patients taking Cytoflavinum, there was a decrease in the frequency and intensity of headache, dizziness, an increase in MMSE score from 26.32 ± 0.86 to 28.05 ± 1.36 (p ≤ 0.05), in MoCA score from 25.35 ± 0.96 to 27.88 ± 1.13 (p ≤ 0.05), decrease in anxiety score from 8.82 ± 1.31 to 5.2 ± 2.82 (p ≤ 0.05) and decrease in HADS depression score from 8.31 ± 1.85 to 4.6 ± 3.15 (p ≤ 0.05).Conclusion. The inclusion of Cytoflavinum in the treatment regimen for patients with chronic CVD helps to reduce the frequency and intensity of headaches and dizziness, improve cognitive functions, and reduce the level of anxiety and depression.

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Abstract TP120: A Novel Potential Therapy in Severe Stroke: Neuroprotective Chlorpromazine/Promethazine Combination in Transient and Permanent Ischemia

Stroke ◽

10.1161/str.48.suppl_1.tp120 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Radhika Rastogi ◽

Xiaokun Geng ◽

Yuchuan Ding

Keyword(s):

Body Temperature ◽

Brain Metabolism ◽

Brain Activity ◽

Artery Occlusion ◽

Neurological Deficits ◽

Therapeutic Effects ◽

Sprague Dawley ◽

Drug Induced ◽

Severe Stroke ◽

Neuroprotective Therapy

Background and Purpose: Previous studies have demonstrated depressive or hibernation-like roles of phenothiazine neuroleptics [combined chlorpromazine and promethazine (C+P)] in brain activity. This ischemic stroke study aimed to establish neuroprotection by reducing oxidative stress and improving brain metabolism through post-ischemic C+P administration. Methods: Sprague-Dawley rats (n=272) were subjected to transient (2 or 4 h) middle cerebral artery occlusion (MCAO) followed by 6 or 24 h reperfusion, or permanent (28 h) MCAO without reperfusion. At 2 h after ischemic onset, rats received either an intraperitoneal (IP) injection of saline or two doses of C+P. Body temperatures, brain infarct volumes, and neurological deficits were examined. Oxidative metabolism and stress were determined by levels of ATP, NADH, and reactive oxygen species (ROS). Protein kinase C-δ (PKC-δ) and Akt expression were determined by Western blotting. Results: In both transient and permanent ischemia models, C+P administration significantly induced a dose-dependent reduction in body temperature and neuroprotection within as early as 5 min and lasting up to 12 h. Body temperature reduction either only slightly or did not enhance C+P-induced neuroprotection, as determined by infarct volumes and neurological deficits post-stroke. C+P therapy improved brain metabolism as determined by increased ATP levels and NADH activity, as well as diminished ROS production. These therapeutic effects were associated with alterations in PKC-δ and Akt protein expression. Conclusions: C+P treatments conferred neuroprotection in severe stroke models by suppressing the damaging cascade of metabolic events, most likely independent of drug-induced hypothermia. These findings may direct us towards the development of an efficacious, practical, and accessible neuroprotective therapy in stroke patients.

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