scholarly journals Delayed reduction in hippocampal postsynaptic density protein-95 expression temporally correlates with cognitive dysfunction following controlled cortical impact in mice

2010 ◽  
Vol 113 (6) ◽  
pp. 1195-1201 ◽  
Author(s):  
Chandramohan Wakade ◽  
Sangeetha Sukumari-Ramesh ◽  
Melissa D. Laird ◽  
Krishnan M. Dhandapani ◽  
John R. Vender
Keyword(s):  
Cerebral Cortex ◽  
Brain Injury ◽  
Learning And Memory ◽  
Head Trauma ◽  
Postsynaptic Density ◽  
Scaffolding Protein ◽  
Specific Marker ◽  
Causative Role ◽  
Clinical Prognosis ◽  
Postsynaptic Density Protein

Object Traumatic brain injury (TBI) induces significant neurological damage, including deficits in learning and memory, which contribute to a poor clinical prognosis. Treatment options to limit cognitive decline and promote neurological recovery are lacking, in part due to a poor understanding of the secondary or delayed processes that contribute to brain injury. In the present study, the authors characterized the temporal and spatial changes in the expression of postsynaptic density protein-95 (PSD-95), a key scaffolding protein implicated in excitatory synaptic signaling, after controlled cortical impacts in mice. Neurological injury, as assessed by the open-field activity test and the novel object recognition test, was compared with changes in PSD-95 expression. Methods Adult male CD-1 mice were subjected to controlled cortical impacts to simulate moderate TBI in humans. The spatial and temporal expression of PSD-95 was analyzed in the cerebral cortex and hippocampus at various time points following injury and sham operations. Neurological assessments were performed to compare changes in PSD-95 with cognitive deficits. Results A significant decrease in PSD-95 expression was observed in the ipsilateral hippocampus beginning on Day 7 postinjury. The loss of PSD-95 corresponded with a concomitant reduction in immunoreactivity for NeuN (neuronal nuclei), a neuron-specific marker. Aside from the contused cortex, a significant loss of PSD-95 immunoreactivity was not observed in the cerebral cortex. The delayed loss of hippocampal PSD-95 directly correlated with the onset of behavioral deficits, suggesting a possible causative role for PSD-95 in behavioral abnormalities following head trauma. Conclusions A delayed loss of hippocampal synapses was observed following head trauma in mice. These data may suggest a cellular mechanism to explain the delayed learning and memory deficits in humans after TBI and provide a potential framework for further testing to implicate PSD-95 as a clinically relevant therapeutic target.

scholarly journals Postsynaptic density protein 95 (PSD-95) is transported by KIF5 to dendritic regions

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Ki-Seo Yoo ◽  
Kina Lee ◽  
Jun-Young Oh ◽  
Hyoeun Lee ◽  
Hyungju Park ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Postsynaptic Density ◽  
Scaffolding Protein ◽  
Synaptic Localization ◽  
Conventional Kinesin ◽  
Dose Dependent ◽  
Postsynaptic Density Protein

AbstractPostsynaptic density protein 95 (PSD-95) is a pivotal postsynaptic scaffolding protein in excitatory neurons. Although the transport and regulation of PSD-95 in synaptic regions is well understood, dendritic transport of PSD-95 before synaptic localization still remains to be clarified. To evaluate the role of KIF5, conventional kinesin, in the dendritic transport of PSD-95 protein, we expressed a transport defective form of KIF5A (ΔMD) that does not contain the N-terminal motor domain. Expression of ΔMD significantly decreased PSD-95 level in the dendrites. Consistently, KIF5 was associated with PSD-95 in in vitro and in vivo assays. This interaction was mediated by the C-terminal tail regions of KIF5A and the third PDZ domain of PSD-95. Additionally, the ADPDZ3 (the association domain of NMDA receptor and PDZ3 domain) expression significantly reduced the levels of PSD-95, glutamate receptor 1 (GluA1) in dendrites. The association between PSD-95 and KIF5A was dose-dependent on Staufen protein, suggesting that the Staufen plays a role as a regulatory role in the association. Taken together, our data suggest a new mechanism for dendritic transport of the AMPA receptor-PSD-95.

scholarly journals Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats

2018 ◽  
Vol 39 (8) ◽  
pp. 1588-1601 ◽  
Author(s):  
Zhifeng Wang ◽  
Zhouqing Chen ◽  
Junjie Yang ◽  
Ziying Yang ◽  
Jia Yin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Nmda Receptor ◽  
Intracerebral Hemorrhage ◽  
Neuronal Death ◽  
Postsynaptic Density ◽  
Synaptic Function ◽  
Learning Ability ◽  
Receptor Interaction ◽  
Secondary Brain Injury ◽  
Postsynaptic Density Protein

Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1–neuroligin-1 to form a complex and participates in maintaining synaptic function. In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1–neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD95 inhibitor Tat-NR2B9c effectively inhibited the interaction between PSD95 and NR2B-nNOS, and promoted the formation of neurexin-1–nueuroligin-1-PSD95 complex. In addition, Tat-NR2B9c treatment significantly reduced neuronal death and degeneration and matrix metalloproteinase 9 activity, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats. Inhibition of the formation of PSD95-NR2B-nNOS complex can rescue secondary brain injury and behavioral cognitive impairment after ICH. PSD95 is expected to be a target for improving the prognosis of patients with ICH.

Head Trauma in a Community-Based Sample of Victims of Intimate Partner Violence: Prevalence, Mechanisms of Injury and Symptom Presentation

2021 ◽  
pp. 088626052110163
Author(s):  
Jessica E. Meyer ◽  
Varna Jammula ◽  
Peter A. Arnett
Keyword(s):  
Intimate Partner Violence ◽  
Brain Injury ◽  
Head Trauma ◽  
Partner Violence ◽  
Physical Violence ◽  
Structured Interview ◽  
Intimate Partner ◽  
Difficulty Breathing ◽  
History Of ◽  
Subconcussive Head Trauma

Objective. The present study aimed to explore the prevalence of subconcussive head trauma, traumatic brain injury (TBI), potential hypoxic events, and hypoxic brain injury (HBI) in victims of physical intimate partner violence (IPV). The study also aimed to characterize the injury presentation and mechanisms of injury in this population. Method. A group of 47 female participants with a history of at least one relationship that included physical violence completed a structured interview assessing for subconcussive hits, TBI, and HBI. Participants ranged in age from 19 to 55, and had an average of 15.3 years of education. Forty-four participants completed the structured interview in person and three participants completed the interview over the phone. Results. The majority of participants reported sustaining at least one impact to the head and approximately half of the participants sustained at least one impact that resulted in a mild TBI. Approximately half of the participants experienced at least one incident of having difficulty breathing due to a violent act from their partner, and approximately one-third of participants reported symptoms consistent with mild HBI. The most common mechanisms of injury were being hit with a closed fist and being strangled. Conclusions. The high levels of head trauma observed in this study highlight the need for clinical and community providers to screen victims of physical IPV for head trauma. The unique characteristics of this population (female sex, high frequency of injuries, and presence of HBIs) indicate that research evaluating the cognitive effects of injuries in this population is needed.

Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density

1995 ◽  
Vol 32 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Tae-Wan Kim ◽  
Kuo Wu ◽  
Jia-Ling Xu ◽  
Geoff McAuliffe ◽  
Rudolph E. Tanzi ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Postsynaptic Density ◽  
Selective Localization

scholarly journals Biomechanics of Traumatic Brain Injury: Influences of the Morphologic Heterogeneities of the Cerebral Cortex

2008 ◽  
Vol 36 (7) ◽  
pp. 1203-1215 ◽  
Author(s):  
R.J.H. Cloots ◽  
H.M.T. Gervaise ◽  
J.A.W. van Dommelen ◽  
M.G.D. Geers
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebral Cortex ◽  
Brain Injury

The mean platelet volume is decreased in patients with mild head trauma and brain injury

2013 ◽  
Vol 24 (7) ◽  
pp. 780-783 ◽  
Author(s):  
Giuseppe Lippi ◽  
Andrea Carbucicchio ◽  
Mario Benatti ◽  
Gianfranco Cervellin
Keyword(s):  
Brain Injury ◽  
Head Trauma ◽  
Mean Platelet Volume ◽  
Platelet Volume ◽  
The Mean

Development of a de novo arteriovenous malformation after severe traumatic brain injury

2014 ◽  
Vol 14 (4) ◽  
pp. 418-420 ◽  
Author(s):  
Brandon A. Miller ◽  
David I. Bass ◽  
Joshua J. Chern
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebral Cortex ◽  
Brain Injury ◽  
Arteriovenous Malformation ◽  
Severe Traumatic Brain Injury ◽  
Arteriovenous Malformations ◽  
De Novo ◽  
First Report ◽  
Congenital Lesions

Arteriovenous malformations (AVMs) are typically considered congenital lesions, although there is growing evidence for de novo formation of these lesions as well. The authors present the case of an AVM in the same cerebral cortex that had been affected by a severe traumatic brain injury (TBI) more than 6 years earlier. To the best of the authors' knowledge, this is the first report attributing the formation of an AVM directly to TBI.

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