Parkinsonism and cerebrovascular disease

Narasimhan, Manisha; Schwartz, Raymond; Halliday, Glenda M.

doi:10.1016/j.jns.2021.120011

Cited by 19 publications

(5 citation statements)

References 213 publications

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“…The incidence of cerebrovascular disease is increasing year by year, and its disability rate and mortality rate are high, but the clinical treatment effect is not satisfactory [ 18 , 19 ]. As an important signaling pathway in cells, the RhoA-ROCK signaling pathway mediates many physiological and pathological processes of nerve cells, such as cell extension, contraction, and regeneration after injury [ 20 , 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Protection against Hypoxia-Reoxygenation Injury of Hippocampal Neurons by H2S via Promoting Phosphorylation of ROCK2 at Tyr722 in Rat Model

Meng

Chen

et al. 2022

Molecules

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The RhoA-ROCK signaling pathway is associated with the protective effects of hydrogen sulfide (H2S) against cerebral ischemia. H2S protects rat hippocampal neurons (RHNs) against hypoxia-reoxygenation (H/R) injury by promoting phosphorylation of RhoA at Ser188. However, effect of H2S on the phosphorylation of ROCK2-related sites is unclear. The present study was designed to investigate whether H2S can play a role in the phosphorylation of ROCK2 at Tyr722, and explore whether this role mediates the protective effect of H/R injury in RHNs. Prokaryotic recombinant plasmids ROCK2wild-pGEX-6P-1 and ROCK2Y722F-pGEX-6P-1 were constructed and transfected into E. coli in vitro, and the expressed protein, GST-ROCK2wild and GST-ROCK2Y722F were used for phosphorylation assay in vitro. Eukaryotic recombinant plasmids ROCK2Y722-pEGFP-N1 and ROCK2Y722F-pEGFP-N1 as well as empty plasmid were transfected into the RHNs. Western blot assay and whole-cell patch-clamp technique were used to detect phosphorylation of ROCK2 at Tyr722 and BKCa channel current in the RHNs, respectively. Cell viability, leakages of intracellular enzymes lactate dehydrogenase (LDH), and nerve-specific enolase (NSE) were measured. The H/R injury was indicated by decrease of cell viability and leakages of intracellular LDH and NSE. The results of Western blot have shown that NaHS, a H2S donor, significantly promoted phosphorylation of GST-ROCK2wild at Tyr722, while no phosphorylation of GST-ROCK2Y722F was detected. The phosphorylation of ROCK2wild promoted by NaHS was also observed in RHNs. NaHS induced more potent effects on protection against H/R injury, phosphorylation of ROCK2 at Tyr722, inhibition of ROCK2 activity, as well as increase of the BKCa current in the ROCK2Y722-pEGFP-N1-transfected RHNs. Our results revealed that H2S protects the RHNs from H/R injury through promoting phosphorylation of ROCK2 at Tyr722 to inhibit ROCK2 activity and potentially by opening channel currents.

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Section: Discussionmentioning

confidence: 99%

Protection against Hypoxia-Reoxygenation Injury of Hippocampal Neurons by H2S via Promoting Phosphorylation of ROCK2 at Tyr722 in Rat Model

Meng

Chen

et al. 2022

Molecules

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“…and other atherosclerotic diseases (e.g., myocardial infarction/ischemic cardiac failure, peripheral artery disease [atherosclerosis obliterans]/foot amputation, and chronic kidney disease/hemodialysis). WMD is the major source of bladder dysfunction (vascular incontinence, 20 overactive bladder syndrome) and gait difficulty (vascular parkinsonism 21,22 ; slow, short stepped gait often associated with an ataxic component), although the grade of dementia (vascular dementia 22 ) in individuals with WMD is mild (the Mini‐Mental State Examination [MMSE] score is usually >15/30, normal >24/30, in patients with four of 0–4 WMD imaging scale) 19 . It is also reported that cognitive function declined to 0.5–1.0 SD (standard deviation) in patients with three of 0–3 WMD imaging scale 23 ; and MMSE declined to 18.7/30 in moderate WMD imaging abnormality 24,25 …”

Section: Brain and Peripheral Nerve Diseases In Older Individualsmentioning

confidence: 99%

Autonomic dysfunction in older individuals: The contributions of multiple brain diseases and diabetes

Sakakibara

Sawai

Ogata

et al. 2022

Neurology & Clinical Neurosc

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The populations of older individuals (age >60 years old) continue to increase worldwide from 400 million in 1980 to 1050 million in 2020, 1 necessitating increases in medical care, particularly for the disorders that develop with age. 2 Geriatric syndrome (symptoms that are commonly seen in older individuals) includes dementia/delirium, 3 gait difficulty/fall 4 /aspiration, 5 and autonomic dysfunction. 1 Among the geriatric syndrome, the brain is contributing to dementia and gait difficulty. 3 Autonomic dysfunctions such as orthostatic hypotension, 2 overactive bladder, and constipation also increase with age. However, autonomic dysfunction in older populations has not been fully delineated, and it is suspected that neurologic etiologies might underlie this condition. 3 This review briefly summarizes (i) the brain and peripheral nerve diseases that are common in older populations; (ii) the mechanisms and management/care of autonomic dysfunction.

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“…Parkinsonism is proposed to emerge secondary to disruption of nigrostriatal circuitry—in particular, impaired functioning or loss of substantia nigra (SN) dopaminergic neurons . Although parkinsonism is most commonly associated with α-synuclein accumulation in Lewy body disease (LBD), it is also observed in tauopathies, such as progressive supranuclear palsy and postencephalitic parkinsonism, and has been associated with cerebrovascular disease …”

Section: Introductionmentioning

confidence: 99%

Substantia Nigra Pathology, Contact Sports Play, and Parkinsonism in Chronic Traumatic Encephalopathy

Adams,

Kirsch,

Calderazzo

et al. 2024

JAMA Neurol

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ImportanceParkinsonism is associated with traumatic brain injury and chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head impact (RHI) exposure, but the neuropathologic substrates that underlie parkinsonism in individuals with CTE are yet to be defined.ObjectiveTo evaluate the frequency of parkinsonism in individuals with CTE and the association of RHI and neuropathologic substrates with parkinsonism in these individuals.Design, Setting, and ParticipantsThis cross-sectional study included brain donors with neuropathologically diagnosed CTE without other significant neurodegenerative disease and with information on parkinsonism from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank between July 2015 and May 2022.ExposureYears of contact sports participation as a proxy for RHI.Main Outcomes and MeasuresThe main outcomes were frequency of parkinsonism in individuals with CTE and associations between (1) RHI with substantia nigra (SN) Lewy bodies (LBs) and neurofibrillary tangles (NFTs); (2) LBs, NFTs, and arteriolosclerosis with SN neuronal loss; and (3) SN neuronal loss, LBs, NFTs, and arteriolosclerosis with parkinsonism, tested by age-adjusted logistic regressions.ResultsOf 481 male brain donors with neuropathologically diagnosed CTE, parkinsonism occurred frequently in individuals with CTE (119 [24.7%]; 362 [75.3%] did not have parkinsonism). Participants with parkinsonism had a higher mean (SD) age at death (71.5 [13.0] years) than participants without parkinsonism (54.1 [19.3] years) (P &lt; .001) and higher rates of dementia (104 [87.4%] vs 105 [29.0%]), visual hallucinations (45 [37.8%] vs 51 [14.1%]), and probable rapid eye movement sleep behavior disorder (52 [43.7%] vs 58 [16.0%]) (P &lt; .001 for all). Participants with parkinsonism had a more severe CTE stage (eg, stage IV: 35 [29.4%] vs 39 [10.8%]) and nigral pathology than those without parkinsonism (NFTs: 50 of 117 [42.7%] vs 103 of 344 [29.9%]; P = .01; neuronal loss: 61 of 117 [52.1%] vs 59 of 344 [17.1%]; P &lt; .001; and LBs: 28 of 116 [24.1%] vs 20 of 342 [5.8%]; P &lt; .001). Years of contact sports participation were associated with SN NFTs (adjusted odds ratio [AOR], 1.04; 95% CI, 1.00-1.07; P = .03) and neuronal loss (AOR, 1.05; 95% CI, 1.01-1.08; P = .02). Nigral neuronal loss (AOR, 2.61; 95% CI, 1.52-4.47; P &lt; .001) and LBs (AOR, 2.29; 95% CI, 1.15-4.57; P = .02) were associated with parkinsonism. However, SN neuronal loss was associated with SN LBs (AOR, 4.48; 95% CI, 2.25-8.92; P &lt; .001), SN NFTs (AOR, 2.51; 95% CI, 1.52-4.15; P &lt; .001), and arteriolosclerosis (AOR, 2.27; 95% CI, 1.33-3.85; P = .002). In American football players, regression analysis demonstrated that SN NFTs and neuronal loss mediated the association between years of play and parkinsonism in the context of CTE (β, 0.012; 95% CI, 0.001-0.038).Conclusions and RelevanceIn this cross-sectional study of contact sports athletes with CTE, years of contact sports participation were associated with SN tau pathology and neuronal loss, and these pathologies were associated with parkinsonism. Repetitive head impacts may incite neuropathologic processes that lead to symptoms of parkinsonism in individuals with CTE.

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Parkinsonism and cerebrovascular disease

Cited by 19 publications

References 213 publications

Protection against Hypoxia-Reoxygenation Injury of Hippocampal Neurons by H2S via Promoting Phosphorylation of ROCK2 at Tyr722 in Rat Model

Protection against Hypoxia-Reoxygenation Injury of Hippocampal Neurons by H2S via Promoting Phosphorylation of ROCK2 at Tyr722 in Rat Model

Autonomic dysfunction in older individuals: The contributions of multiple brain diseases and diabetes

Substantia Nigra Pathology, Contact Sports Play, and Parkinsonism in Chronic Traumatic Encephalopathy

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