Persistent Region-Dependent Neuroinflammation, Nmda Receptor Loss and Atrophy In An Animal Model of Penetrating Brain Injury

Abstract

Dynamic changes in neuroinflammation and glutamate NMDA receptors (NMDAR) have been noted in traumatic and ischemic brain injury. Aim Here we investigate the time course and regional distribution of these changes and their relationship with atrophy in a rat model of penetrating brain injury. Materials & methods Quantitative autoradiography, with the neuroinflammation marker [3H]PK11195 and the NMDAR antagonist [125I]iodoMK801, was performed on brains of animals subjected to a unilateral wireknife injury at the level of striatum and killed 3 – 60 days later. Regional atrophy was measured by morphometry. Results The injury produced large increases in [3H]PK11195 binding density in cortical and septal regions adjacent to the knife track by day 7, with modest increases in the striatum. [125I]iodoMK801 binding was reduced in cor tical and hippocampal regions showing marked neuroinflammation, which showed marked atrophy at subsequent time points. Conclusion These results indicate that neuroinflammaton and loss of NMDAR precede and predict tissue atrophy in cortical and hippocampal regions.

Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

“…These findings align with previous reports on irradiation induced neuro-inflammation and the ability of neuro-inflammation to spread from the site of injury to relatively remote regions of the central nervous system [ 36 , 44 ].…”

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

“…Research concerning TSPO ligand uptake in animal models of TBI overwhelmingly supports the findings of its role as a microglia/macrophage activator. Specifically, studies have revealed that the increases of BP using 11C-PK11195 can be associated with both the time and type of brain injury [174][175][176]. Investigations using second-generation ligands fully support the results of the increased uptake in different types of trauma but are in contrast with the findings of increases of TSPO expression early after traumatic events [50].…”

[18F]fallypride-PET/CT Analysis of the Dopamine D2/D3 Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection

“…In this study we examined cellular mechanisms of the positive motor effect of intrastriatally injected BoNT-A by [ 18 F]fallypride PET/CT scans in hemi-PD rats, as BoNT-A was previously demonstrated to abolish apomorphine-induced rotational behavior in 6-OHDA-lesioned [ 23 , 24 , 25 , 26 ]. The control group respected the entire surgical procedure as the minimal lesion caused by the insertion of the syringe could lead to changes in receptor binding sites [ 32 , 33 ]. We did not include an experimental group studying BoNT-A in sham-lesioned rats in our design as we assumed that BoNT-A would not alter per se the expression of D 2 /D 3 receptors.…”