Long-term potentiation deficits and excitability changes following traumatic brain injury

1995 ◽  
Vol 106 (2) ◽  
Author(s):  
ThomasM. Reeves ◽  
BruceG. Lyeth ◽  
JohnT. Povlishock
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Long Term Potentiation ◽  
Term Potentiation

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 Proteasome and Autophagy-Mediated Impairment of Late Long-Term Potentiation (l-LTP) after Traumatic Brain Injury in the Somatosensory Cortex of Mice

2019 ◽  
Vol 20 (12) ◽  
pp. 3048 ◽  
Author(s):  
Feldmann ◽  
Le Prieult ◽  
Felzen ◽  
Thal ◽  
Engelhard ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Degradation ◽  
Long Term Potentiation ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Ipsilateral Hemisphere ◽  
Term Potentiation ◽  
Theta Burst

Traumatic brain injury (TBI) can lead to impaired cognition and memory consolidation.The acute phase (24–48 h) after TBI is often characterized by neural dysfunction in the vicinity ofthe lesion, but also in remote areas like the contralateral hemisphere. Protein homeostasis is crucialfor synaptic long-term plasticity including the protein degradation systems, proteasome andautophagy. Still, little is known about the acute effects of TBI on synaptic long-term plasticity andprotein degradation. Thus, we investigated TBI in a controlled cortical impact (CCI) model in themotor and somatosensory cortex of mice ex vivo-in vitro. Late long-term potentiation (l-LTP) wasinduced by theta-burst stimulation in acute brain slices after survival times of 1–2 days. Proteinlevels for the plasticity related protein calcium/calmodulin-dependent protein kinase II (CaMKII)was quantified by Western blots, and the protein degradation activity by enzymatical assays. Weobserved missing maintenance of l-LTP in the ipsilateral hemisphere, however not in thecontralateral hemisphere after TBI. Protein levels of CaMKII were not changed but, interestingly,the protein degradation revealed bidirectional changes with a reduced proteasome activity and anincreased autophagic flux in the ipsilateral hemisphere. Finally, LTP recordings in the presence ofpharmacologically modified protein degradation systems also led to an impaired synaptic plasticity:bath-applied MG132, a proteasome inhibitor, or rapamycin, an activator of autophagy, bothadministered during theta burst stimulation, blocked the induction of LTP. These data indicate thatalterations in protein degradation pathways likely contribute to cognitive deficits in the acute phaseafter TBI, which could be interesting for future approaches towards neuroprotective treatmentsearly after traumatic brain injury.

Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in rat

1992 ◽  
Vol 585 (1-2) ◽  
pp. 335-339 ◽  
Author(s):  
S. Miyazaki ◽  
Y. Katayama ◽  
B.G. Lyeth ◽  
L.W. Jenkins ◽  
D.S. DeWitt ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Long Term Potentiation ◽  
Term Potentiation

Ellagic acid prevents cognitive and hippocampal long-term potentiation deficits and brain inflammation in rat with traumatic brain injury

Life Sciences ◽  
2015 ◽  
Vol 124 ◽  
pp. 120-127 ◽  
Author(s):  
Yaghoob Farbood ◽  
Alireza Sarkaki ◽  
Mahin Dianat ◽  
Ali Khodadadi ◽  
Mohammad Khaksari Haddad ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Ellagic Acid ◽  
Long Term Potentiation ◽  
Brain Inflammation ◽  
Term Potentiation

scholarly journals Repeated Mild Traumatic Brain Injury Causes Chronic Neuroinflammation, Changes in Hippocampal Synaptic Plasticity, and Associated Cognitive Deficits

2014 ◽  
Vol 34 (7) ◽  
pp. 1223-1232 ◽  
Author(s):  
Stephanie L Aungst ◽  
Shruti V Kabadi ◽  
Scott M Thompson ◽  
Bogdan A Stoica ◽  
Alan I Faden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Hippocampal Slices ◽  
Neuronal Cell ◽  
Long Term Potentiation ◽  
Cognitive Changes ◽  
Chronic Neuroinflammation ◽  
Term Potentiation

Repeated mild traumatic brain injury (mTBI) can cause sustained cognitive and psychiatric changes, as well as neurodegeneration, but the underlying mechanisms remain unclear. We examined histologic, neurophysiological, and cognitive changes after single or repeated (three injuries) mTBI using the rat lateral fluid percussion (LFP) model. Repeated mTBI caused substantial neuronal cell loss and significantly increased numbers of activated microglia in both ipsilateral and contralateral hippocampus on post-injury day (PID) 28. Long-term potentiation (LTP) could not be induced on PID 28 after repeated mTBI in ex vivo hippocampal slices from either hemisphere. N-Methyl-D-aspartate (NMDA) receptor-mediated responses were significantly attenuated after repeated mTBI, with no significant changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated responses. Long-term potentiation was elicited in slices after single mTBI, with potentiation significantly increased in ipsilateral versus contralateral hippocampus. After repeated mTBI, rats displayed cognitive impairments in the Morris water maze (MWM) and novel object recognition (NOR) tests. Thus, repeated mTBI causes deficits in the hippocampal function and changes in excitatory synaptic neurotransmission, which are associated with chronic neuroinflammation and neurodegeneration.

Hydrogen Sulfide in Physiological and Pathological Mechanisms in Brain

2018 ◽  
Vol 17 (9) ◽  
pp. 654-670 ◽  
Author(s):  
Mohit Kumar ◽  
Rajat Sandhir
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Hydrogen Sulfide ◽  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Scientific Community ◽  
Molecular Targets ◽  
Long Term Potentiation ◽  
Term Potentiation

Background & Objective: Hydrogen sulfide [H2S] has been widely known as a toxic gas for more than 300 years in the scientific community. However, the understanding about this small molecule has changed after the discovery of involvement of H2S in physiological and pathological mechanisms in brain. H2S is a third gasotransmitter and neuromodulator after carbon monoxide [CO] and nitric oxide [NO]. H2S plays an important role in memory and cognition by regulating long-term potentiation [LTP] and calcium homeostasis in neuronal cells. The disturbances in endogenous H2S levels and trans-sulfuration pathway have been implicated in neurodegenerative disorders like Alzheimer’s disease, Parkinson disease, stroke and traumatic brain injury. According to the results obtained from various studies, H2S not only behaves as neuromodulator but also is a potent antioxidant, anti-inflammatory and anti-apoptotic molecule suggesting its neuroprotective potential. Conclusion: Recently, there is an increased interest in developing H2S releasing pharmaceuticals to target various neurological disorders. This review covers the information about the involvement of H2S in neurodegenerative diseases, its molecular targets and its role as potential therapeutic molecule.

scholarly journals High Il-1β Serum as a Predictor of Decreased Cognitive Function in Mild Traumatic Brain Injury Patients

2018 ◽  
Vol 6 (9) ◽  
pp. 1674-1677
Author(s):  
Dewa Putu Gede Purwa Samatra ◽  
Ni Made Dwita Pratiwi ◽  
I Putu Eka Widyadharma
Keyword(s):  
Traumatic Brain Injury ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Cognitive Function ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Long Term Potentiation ◽  
High Serum ◽  
Mild Tbi ◽  
Term Potentiation

BACKGROUND: Traumatic brain injury (TBI) exerts a significant impact on society with regards to physical, affective, and cognitive impairment. The consequent cognitive sequelae include a problem in memory, attention, concentration, and processing speed. Following traumatic brain injury, inflammatory response developed, characterised by increased interleukin 1-β (IL-1β) levels in the blood. IL 1-β at pathophysiological concentration has been reported to cause an inhibition of the expression of long-term potentiation (LTP) in the areas CA1, CA3, and dentate gyrus of the hippocampus. AIM: This study aims to determine whether high IL-1β serum is a predictor of decreased cognitive function in mild TBI. METHODS: This is a prospective cohort study conducted at the emergency room, surgical and neurologic ward at Sanglah Hospital from November 2017 until January 2018. As many as thirty-five mild TBI with normal IL-1β serum (< 0.0565 pg/ml) and thirty-five of those with high IL-1β serum (≥ 0.0565 pg/ml) subjects were included within the corresponding period. The decrease of cognition after trauma was measured seven days later. RESULTS: This study demonstrated that group with high IL-1β serum levels were at higher risk of suffering from cognitive impairment after TBI when compared with the group with normal IL-1β serum levels (RR = 2.6; 95% CI 1.49-4.55, p < 0.001). CONCLUSION: Mild TBI with high serum IL-1β levels were more than twice likely to experience decreased cognitive function than those with normal IL-1β levels.

scholarly journals Biologic Effect of Hydrogen Sulfide and Its Role in Traumatic Brain Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiaxin Zhang ◽  
Shaoyi Zhang ◽  
Haiyan Shan ◽  
Mingyang Zhang
Keyword(s):  
Traumatic Brain Injury ◽  
Hydrogen Sulfide ◽  
Brain Injury ◽  
Therapeutic Potential ◽  
Long Term Potentiation ◽  
Secondary Brain Injury ◽  
Term Potentiation ◽  
Great Hope ◽  
Biologic Effects ◽  
Physiological Dose

Ever since endogenous hydrogen sulfide (H2S) was found in mammals in 1989, accumulated evidence has demonstrated that H2S functions as a novel neurological gasotransmitter in brain tissues and may play a key role in traumatic brain injury. It has been proved that H2S has an antioxidant, anti-inflammatory, and antiapoptosis function in the neuron system and functions as a neuroprotective factor against secondary brain injury. In addition, H2S has other biologic effects such as regulating the intracellular concentration of Ca2+, facilitating hippocampal long-term potentiation (LTP), and activating ATP-sensitive K channels. Due to the toxic nature of H2S when exceeding the physiological dose in the human body, only a small amount of H2S-related therapies was applied to clinical treatment. Therefore, it has huge therapeutic potential and has great hope for recovering patients with traumatic brain injury.

scholarly journals Intranasal delivery of interleukin-4 attenuates chronic cognitive deficits via beneficial microglial responses in experimental traumatic brain injury

2021 ◽  
pp. 0271678X2110286
Author(s):  
Hongjian Pu ◽  
Cheng Ma ◽  
Yongfang Zhao ◽  
Yangfan Wang ◽  
Wenting Zhang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Deficits ◽  
Cognitive Functions ◽  
Diffusion Tensor ◽  
Long Term Potentiation ◽  
Interleukin 4 ◽  
Intranasal Delivery ◽  
Arginase 1

Traumatic brain injury (TBI) is commonly followed by long-term cognitive deficits that severely impact the quality of life in survivors. Recent studies suggest that microglial/macrophage (Mi/MΦ) polarization could have multidimensional impacts on post-TBI neurological outcomes. Here, we report that repetitive intranasal delivery of interleukin-4 (IL-4) nanoparticles for 4 weeks after controlled cortical impact improved hippocampus-dependent spatial and non-spatial cognitive functions in adult C57BL6 mice, as assessed by a battery of neurobehavioral tests for up to 5 weeks after TBI. IL-4-elicited enhancement of cognitive functions was associated with improvements in the integrity of the hippocampus at the functional ( e.g., long-term potentiation) and structural levels (CA3 neuronal loss, diffusion tensor imaging of white matter tracts, etc.). Mechanistically, IL-4 increased the expression of PPARγ and arginase-1 within Mi/MΦ, thereby driving microglia toward a global inflammation-resolving phenotype. Notably, IL-4 failed to shift microglial phenotype after TBI in Mi/MΦ-specific PPARγ knockout (mKO) mice, indicating an obligatory role for PPARγ in IL-4-induced Mi/MΦ polarization. Accordingly, post-TBI treatment with IL-4 failed to improve hippocampal integrity or cognitive functions in PPARγ mKO mice. These results demonstrate that administration of exogenous IL-4 nanoparticles stimulates PPARγ-dependent beneficial Mi/MΦ responses, and improves hippocampal function after TBI.

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