scholarly journals Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms

2017 ◽  
Author(s):  
Donal T. Skelly ◽  
Éadaoin W. Griffin ◽  
Carol L. Murray ◽  
Sarah Harney ◽  
Conor O’Boyle ◽  
...  
Keyword(s):  
Working Memory ◽  
Brain Injury ◽  
Cognitive Dysfunction ◽  
Systemic Inflammation ◽  
De Novo ◽  
Hippocampal Slices ◽  
Memory Deficits ◽  
Acute Brain Injury ◽  
Contextual Fear Conditioning

AbstractSystemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Acute episodes of delirium also contribute significantly to rates of long-term cognitive decline, implying that de novo pathology occurs during these acute episodes. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms has not been investigated. Here we show that systemic inflammation, induced by bacterial LPS, produces both working memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100μg/kg) did not affect working memory but robustly impaired contextual fear conditioning (CFC). However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Although LPS-induced deficits still occured in IL-1RI-/- mice, systemic TNF-α was sufficient to induce similar deficits, indicating redundancy among these cytokines. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits despite failing to block brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI-/- dependent-fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but dysfunction leading to neuronal death is mediated by hippocampal IL-1β. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury that may lead to long-term cognitive impairment but that these events are mechanistically dissociable. This would have significant implications for management of cognitive dysfunction and decline during acute illness.

Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome release

2018 ◽  
Vol 119 (1) ◽  
pp. 305-311 ◽  
Author(s):  
Wei Chen ◽  
Yijun Guo ◽  
Wenjin Yang ◽  
Lei Chen ◽  
Dabin Ren ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gap Junction ◽  
Connexin 43 ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Cx43 Expression ◽  
Term Potentiation ◽  
Junction Protein

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using Western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results imply that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release. NEW & NOTEWORTHY We have demonstrated in rat traumatic brain injury (TBI) models that both phosphorylated connexin 43 (p-Cx43) expression and exosome release were elevated in the hippocampus following TBI. The promoted exosome release depends on the phosphorylation of Cx43 and requires ERK signaling activation. Exosome treatment could partially restore the attenuated long-term potentiation. Our results provide new insight for future therapeutic direction on the functional recovery of TBI by promoting p-Cx43-dependent exosome release but limiting the gap junction-mediated bystander effect.

scholarly journals Quality of life in patients with mild acute brain injury and their carers’ needs in Greece

2021 ◽  
Vol 9 (1) ◽  
pp. 39
Author(s):  
Evgenia Stasinopoulou ◽  
Margarita Giannakopoulou ◽  
Georgios Fildisis ◽  
Maria Kalafati ◽  
Chryssoula Leomonidou
Keyword(s):  
Quality Of Life ◽  
Brain Injury ◽  
Social Life ◽  
Well Being ◽  
Acute Brain Injury ◽  
Support Network ◽  
Family Needs ◽  
Rehabilitation Centers

Background: Investigating quality of life (QoL) is of crucial importance for the scientific community as it could function not only as an indicator of prognosis and post-traumatic clinical and psychological changes in patients who have suffered from acute brain injury (ABI), but also as an indicator of the effectiveness of their treatment and social rehabilitation. In addition, it can highlight changes in the carer’s health, social life and well-being. This study examined the QoL of patients following ABI and the needs of their carers.Material and methodology: This study was conducted in patients suffering from ABI, who were admitted to the General Hospital of Attica “KAT” and to the National Rehabilitation Center and on their carers. Data collection including demographics and Quality of Life After Brain Injury Questionnaire (QOLIBRI) and the Family Needs Questionnaire (FNQ) was performed during patients’ rehabilitation, while six months after release, a follow-up survey was conducted using the same questionnaires. Statistical analysis of data was performed using SPSS.Results: We analysed 50 patients with mild ABI (GCS ≥ of 13/15) during rehabilitation and six months after release and found that their QoL improves and is positively related to improvement of health status (i.e. in terms of thinking ability, QoL improves from r = 2.33, p < .01 to r = 3.37, p < .001). We also found that “Age” has the greatest impact on the patient’s progress for recovery and the general QoL after ABI (r = -0.423, p < .01). In addition, it was found that carers of patients with ABI are confronted with the burden of care, while they record both fulfilled and unmet needs regarding their individual needs (i.e. only for 30% of the sample the need for help in preparing them for the worst is met).Conclusions: Our study confirms previous findings that underline that ABI has a major impact on QoL of both patients and their carers providing them with long-term daily care. Although it has been found that over time there is an improvement in the QoL of patients with ABI, the absence of an official support network for carers from public health system, hospitals and rehabilitation centers may adversely affect the QoL of patients and their carers. Therefore, more structured, long-term family-wide monitoring and support is needed, focusing on identifying those at risk of social isolation and incomplete social networking.

scholarly journals RO-09LITHIUM PREVENTS IRRADIATION-INDUCED BRAIN INJURY, HYPOTHYROIDISM AND LONG TERM COGNITIVE DYSFUNCTION IN THE YOUNG RAT

2016 ◽  
Vol 18 (suppl 3) ◽  
pp. iii160.5-iii161
Author(s):  
Kai Zhou ◽  
Cuicui Xie ◽  
Yaodaong Zhang ◽  
Tao Li ◽  
Changlian Zhu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cognitive Dysfunction ◽  
Young Rat

scholarly journals Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium

2012 ◽  
Vol 33 (3) ◽  
pp. 603-616.e3 ◽  
Author(s):  
Carol Murray ◽  
David J. Sanderson ◽  
Chris Barkus ◽  
Robert M.J. Deacon ◽  
J. Nicholas P. Rawlins ◽  
...  
Keyword(s):  
Working Memory ◽  
Systemic Inflammation ◽  
Memory Deficits

Working Memory Deficits following Traumatic Brain Injury in the Rat

1996 ◽  
Vol 13 (6) ◽  
pp. 317-323 ◽  
Author(s):  
ROBERT J. HAMM ◽  
MEREDITH D. TEMPLE ◽  
BRIAN R. PIKE ◽  
DIANNE M. O'DELL ◽  
DEANNA L. BUCK ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Working Memory ◽  
Brain Injury ◽  
Memory Deficits

scholarly journals Differential Inhibition of E-S Potentiation and Long-term Potentiation by Cell-derived and Arctic Amyloid Beta

2019 ◽  
Author(s):  
Adrienne L. Orr ◽  
Jason K. Clark ◽  
Daniel V. Madison
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Hippocampal Slices ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Amyloid Beta Peptide ◽  
Term Potentiation ◽  
Beta Peptide

AbstractSoluble oligomers of amyloid-beta peptide (Abeta) have been implicated in the onset of memory deficits in Alzheimer’s disease, perhaps due to their reported ability to impair long-term potentiation (LTP) of synaptic strength. We previously showed the effect of Abeta on LTP depends on the strength of LTP induction. Furthermore, Abeta affects EPSP-Spike (E-S) potentiation more robustly than LTP, suggesting that E-S potentiation may be equally important to learning and memory in the context of Alzheimer’s disease. Here we extend our findings to two additional forms of Abeta that form higher concentrations of soluble Abeta oligomers and show that they also affect E-S potentiation at induction strengths where there is no effect on LTP in hippocampal slices.

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