Rhein Protects Against Neurological Deficits After Traumatic Brain Injury in Mice via Inhibiting Neuronal Pyroptosis

Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired blood–brain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury (TBI) is an important cause of disability and mortality worldwide, and neurovascular inflammation plays an important role in the TBI pathophysiology. In the present study, we aimed to test the hypothesis that A2KO promotes pro-inflammatory response in the brain and worsens neurobehavioral outcomes after TBI. TBI was conducted by a controlled cortical impact (CCI) device in mice. Our experimental results showed AnxA2 expression was significantly up-regulated in response to TBI at day three post-TBI. We also found more production of pro-inflammatory cytokines in the A2KO mouse brain, while there was a significant increase of inflammatory adhesion molecules mRNA expression in isolated cerebral micro-vessels of A2KO mice compared with wild-type (WT) mice. Consistently, the A2KO mice brains had a significant increase in leukocyte brain infiltration at two days after TBI. Importantly, A2KO mice had significantly worse sensorimotor and cognitive function deficits up to 28 days after TBI and significantly larger brain tissue loss. Therefore, these results suggested that AnxA2 deficiency results in exacerbated early neurovascular pro-inflammation, which leads to a worse long-term neurologic outcome after TBI.

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Concepts in Periodic Discharges: A Descriptive Study

International Journal of Epilepsy ◽

10.1055/s-0039-1692732 ◽

2018 ◽

Vol 05 (02) ◽

pp. 068-074

Author(s):

Laxmi Khanna ◽

Nandini Agarwal ◽

Sabita Kandel

Keyword(s):

Traumatic Brain Injury ◽

Status Epilepticus ◽

Brain Injury ◽

Multiorgan Failure ◽

Autoimmune Encephalitis ◽

Abnormal Behavior ◽

Neurological Deficits ◽

Eeg Monitoring ◽

Herpes Encephalitis ◽

Periodic Discharges

Abstract Introduction Periodic discharges are now known as the ictal–interictal continuum and represent ongoing injury in acute or chronic neurological illnesses. Objective The aim of our study was to identify periodic discharges in patients who have undergone continuous bedside electroencephalography (EEG) monitoring and to classify the EEG according to the current American Clinical Neurophysiology Society terminology. Materials and Methods The continuous bedside EEG records of intensive care patients admitted from August 2017 to July 2018 were analyzed. The clinical spectrum, the treatment, and outcome of each of these patients were monitored. Results Fifty cases of periodic discharges (11 children, 39 adults) were identified over 1 year from 2017 to 2018. The clinical presentation included 32% seizures, 16% status epilepticus, 20% coma, 16% fever with altered sensorium, 8% abnormal behavior, 4% strokes, and 4% traumatic brain injury. The diagnosis was 20% autoimmune encephalitis, 8% herpes encephalitis, 20% multiorgan failure, 4% traumatic brain injury, 16% status epilepticus, 16% posthypoxic encephalopathy, 4% strokes, 4% intracerebral bleeds, 4% meningitis, and 4% severe dementia. Lateralized periodic discharges were identified in 20%, bilateral independent periodic discharges in 20%, and generalized periodic discharges in 60%. Fifty-six percent patients recovered with residual neurological deficits and 44% succumbed to their illness. Conclusions Continuous bedside EEG monitoring has revolutionized the approach to seizures in critically ill patients. Despite a vigilant approach and diligent diagnosis of these abnormal rhythms, the mortality rate was 20% in patients with lateralized periodic discharges and 60% with bilateral and generalized periodic discharges (p ≤ 0.05).

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Lack of mitochondrial ferritin aggravated neurological deficits via enhancing oxidative stress in a traumatic brain injury murine model

Bioscience Reports ◽

10.1042/bsr20170942 ◽

2017 ◽

Vol 37 (6) ◽

Cited By ~ 9

Author(s):

Ligang Wang ◽

Libo Wang ◽

Zhibo Dai ◽

Pei Wu ◽

Huaizhang Shi ◽

...

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Knockout Mice ◽

Brain Injuries ◽

Brain Infarction ◽

Neurological Deficits ◽

Important Correlation ◽

The Brain ◽

And Oxidative Stress

Oxidative stress has been strongly implicated in the pathogenesis of traumatic brain injury (TBI). Mitochondrial ferritin (Ftmt) is reported to be closely related to oxidative stress. However, whether Ftmt is involved in TBI-induced oxidative stress and neurological deficits remains unknown. In the present study, the controlled cortical impact model was established in wild-type and Ftmt knockout mice as a TBI model. The Ftmt expression, oxidative stress, neurological deficits, and brain injury were measured. We found that Ftmt expression was gradually decreased from 3 to 14 days post-TBI, while oxidative stress was gradually increased, as evidenced by reduced GSH and superoxide dismutase levels and elevated malondialdehyde and nitric oxide levels. Interestingly, the extent of reduced Ftmt expression in the brain was linearly correlated with oxidative stress. Knockout of Ftmt significantly exacerbated TBI-induced oxidative stress, intracerebral hemorrhage, brain infarction, edema, neurological severity score, memory impairment, and neurological deficits. However, all these effects in Ftmt knockout mice were markedly mitigated by pharmacological inhibition of oxidative stress using an antioxidant, N-acetylcysteine. Taken together, these results reveal an important correlation between Ftmt and oxidative stress after TBI. Ftmt deficiency aggravates TBI-induced brain injuries and neurological deficits, which at least partially through increasing oxidative stress levels. Our data suggest that Ftmt may be a promising molecular target for the treatment of TBI.

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Exercise attenuates neurological deficits by stimulating a critical HSP70/NF-κB/IL-6/synapsin I axis in traumatic brain injury rats

Journal of Neuroinflammation ◽

10.1186/s12974-017-0867-9 ◽

2017 ◽

Vol 14 (1) ◽

Cited By ~ 18

Author(s):

Chung-Ching Chio ◽

Hung-Jung Lin ◽

Yu-Feng Tian ◽

Yu-Chieh Chen ◽

Mao-Tsun Lin ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neurological Deficits ◽

Synapsin I

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TLR4 signal ablation attenuated neurological deficits by regulating microglial M1/M2 phenotype after traumatic brain injury in mice

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2017.06.006 ◽

2017 ◽

Vol 310 ◽

pp. 38-45 ◽

Cited By ~ 40

Author(s):

Xiaolong Yao ◽

Shengwen Liu ◽

Wei Ding ◽

Pengjie Yue ◽

Qian Jiang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neurological Deficits ◽

M2 Phenotype

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Blood brain barrier dysfunction and delayed neurological deficits in mild traumatic brain injury induced by blast shock waves

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2014.00232 ◽

2014 ◽

Vol 8 ◽

Cited By ~ 13

Author(s):

Ashok K. Shetty ◽

Vikas Mishra ◽

Maheedhar Kodali ◽

Bharathi Hattiangady

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Shock Waves ◽

Blood Brain Barrier ◽

Mild Traumatic Brain Injury ◽

Brain Barrier ◽

Neurological Deficits ◽

Barrier Dysfunction ◽

Blood Brain

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Near Infrared Transcranial Laser Therapy Applied at Various Modes to Mice following Traumatic Brain Injury Significantly Reduces Long-Term Neurological Deficits

Journal of Neurotrauma ◽

10.1089/neu.2011.2062 ◽

2012 ◽

Vol 29 (2) ◽

pp. 401-407 ◽

Cited By ~ 39

Author(s):

Amir Oron ◽

Uri Oron ◽

Jackson Streeter ◽

Luis De Taboada ◽

Alexander Alexandrovich ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Laser Therapy ◽

Near Infrared ◽

Neurological Deficits

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THE IMPORTANCE OF CENTRAL CHOLINERGIC SYSTEMS ACTIVATION IN TRAUMATIC BRAIN INJURY

Medical Science of Ukraine (MSU) ◽

10.32345/2664-4738.3.2020.1 ◽

2020 ◽

Vol 16 (3) ◽

pp. 3-8

Author(s):

S.V. Ziablitsev ◽

S.O. Khudoley

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neurological Deficit ◽

Physiological Saline ◽

Neurological Deficits ◽

Control Group ◽

Post Traumatic Stress ◽

Acute Period ◽

Cholinergic Systems ◽

Release Of Acetylcholine

Relevance. It is known that in traumatic brain injury (TBI), the activity of the central cholinergic systems (CChS) is inhibited, the release of acetylcholine and the expression of cholinergic receptors decrease. The restoration of cholinoreactivity is an urgent area of research and a possible therapeutic direction. Objective – to determine the effect of CChS activation on mortality, neurological disorders, and the activity of the pituitary-corticoadrenal system (PCAS) in the acute period of TBI. Material and methods. TBI was simulated with a free load’s fall on a fixed animal head. To activate the CChS, rats were injected with choline alfoscerate (gliatilin, 6 mg/kg) before the injury, physiological saline was injected in the control group. Neurological deficits were assessed using the 100-point Todd scale. In blood plasma, 3, 24, 48, and 72 hours after injury, the content of adrenocorticotropic hormone and corticosterone was determined by the enzyme immunoassay method (DSL; USA). The results were statistically processed using the SPSS 11.0, MedStat, MedCalc software. Results. Mortality in the control group was 25.0%, in the group with activation of the CChS there were no lethal cases (p<0.05). The neurological deficit in the group with CChS activation was significantly less pronounced compared to the control at all periods of observation. The hormone content had a similar dynamics: it reached a maximum after 24 hours and recovered after 72 hours, however, upon activation of the CChS, the increase was 1.4-1.5 times less (p<0.05). Thus, the use of choline alfoscerate for modeling the CChS activity led to a decrease in mortality and neurological deficit in the acute period of TBI, which was accompanied by a stabilizing PCAS function. Conclusion. The important role of CChS in the implementation of post-traumatic stress reaction of PCAS, as well as the possibility of its pharmacological correction with choline alfoscerate, was established.

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