Neuroinflammatory Cytokine Response, Neuronal Death and Microglial Proliferation in the Hippocampus of Rats During the Early Period After Lateral Fluid-Percussion-Induced Traumatic Injury of the Neocortex

Abstract Time course of changes in neuroinflammatory processes in the dorsal and ventral hippocampus was studied during the early period after lateral fluid-percussion-induced neocortical traumatic brain injury (TBI) in the ipsilateral and contralateral hemispheres. In the ipsilateral hippocampus, neuroinflammation (increase in expression of pro-inflammatory cytokines) was evident from day 1 after TBI and ceased by day 14, while in the contralateral hippocampus it was mainly limited to the dorsal part on day 1. TBI induced an increase in hippocampal corticosterone level on day 3 bilaterally and an accumulation of Il1b on day 1 in the ipsilateral hippocampus. Activation of microglia was observed from day 7 in different hippocampal areas of both hemispheres. Neuronal cell loss was detected in the ipsilateral dentate gyrus on day 3 and extended to the contralateral hippocampus by day 7 after TBI. The data suggest that TBI results in distant hippocampal damage (delayed neurodegeneration in the dentate gyrus and microglia proliferation in both the ipsilateral and contralateral hippocampus), the time course of this damage being different from that of the neuroinflammatory response.

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Neuroinflammatory Cytokine Response, Neuronal Death, and Microglial Proliferation in the Hippocampus of Rats During the Early Period After Lateral Fluid Percussion-Induced Traumatic Injury of the Neocortex

Molecular Neurobiology ◽

10.1007/s12035-021-02668-4 ◽

2021 ◽

Author(s):

Ilia G. Komoltsev ◽

Liya V. Tret’yakova ◽

Stepan O. Frankevich ◽

Natalia I. Shirobokova ◽

Aleksandra A. Volkova ◽

...

Keyword(s):

Neuronal Death ◽

Traumatic Injury ◽

Early Period ◽

Cytokine Response ◽

Fluid Percussion ◽

Microglial Proliferation ◽

Lateral Fluid Percussion

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MRI Heralds Secondary Nigral Lesion after Brain Ischemia in Mice: A Secondary Time Window for Neuroprotection

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.153 ◽

2015 ◽

Vol 35 (12) ◽

pp. 1903-1909 ◽

Cited By ~ 14

Author(s):

Vincent Prinz ◽

Anna-Maria Hetzer ◽

Susanne Müller ◽

Mustafa Balkaya ◽

Christoph Leithner ◽

...

Keyword(s):

Time Course ◽

Time Window ◽

Neuronal Degeneration ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Cell Loss ◽

Ischemic Lesion ◽

Mk 801 ◽

Delayed Treatment ◽

Secondary Time

Cerebral ischemia in the territory of the middle cerebral artery (MCA) can induce delayed neuronal cell death in the ipsilateral substantia nigra (SN) remote from the primary ischemic lesion. This exofocal postischemic neuronal degeneration (EPND) may worsen stroke outcomes. However, the mechanisms leading to EPND are poorly understood. Here, we studied the time course of EPND via sequential magnetic resonance imaging (MRI) and immunohistochemistry for up to 28 days after 30 minutes occlusion of the MCA (MCAo) and reperfusion in the mouse. Furthermore, the effects of delayed treatment with FK506 and MK-801 on the development of EPND were investigated. Secondary neuronal degeneration in the SN occurred within the first week after MCAo and was characterized by a marked neuronal cell loss on histology. Sequential neuroimaging examinations revealed transient MRI changes, which were detectable as early as day 4 after MCAo and thus heralding histologic evidence of EPND. Treatment with MK-801, an established anti-excitotoxic agent, conferred protection against EPND even when initiated days after the initial ischemic event, which was not evident with FK506. Our findings define a secondary time window for delayed neuroprotection after stroke, which may provide a promising target for the development of novel therapies.

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Neuroinflammation and Neuronal Loss in the Hippocampus Are Associated with Immediate Posttraumatic Seizures and Corticosterone Elevation in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22115883 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5883

Author(s):

Ilia G. Komoltsev ◽

Stepan O. Frankevich ◽

Natalia I. Shirobokova ◽

Aleksandra A. Volkova ◽

Mikhail V. Onufriev ◽

...

Keyword(s):

Neuronal Cell ◽

Neuronal Loss ◽

Cell Loss ◽

Hippocampal Damage ◽

Sham Operation ◽

Nissl Staining ◽

Potential Association ◽

Neuronal Cell Loss ◽

Male Wistar Rats ◽

Posttraumatic Seizures

Hippocampal damage after traumatic brain injury (TBI) is associated with late posttraumatic conditions, such as depression, cognitive decline and epilepsy. Mechanisms of selective hippocampal damage after TBI are not well understood. In this study, using rat TBI model (lateral fluid percussion cortical injury), we assessed potential association of immediate posttraumatic seizures and changes in corticosterone (CS) levels with neuroinflammation and neuronal cell loss in the hippocampus. Indices of distant hippocampal damage (neurodegeneration and neuroinflammation) were assessed using histological analysis (Nissl staining, Iba-1 immunohistochemical staining) and ELISA (IL-1β and CS) 1, 3, 7 and 14 days after TBI or sham operation in male Wistar rats (n = 146). IL-1β was elevated only in the ipsilateral hippocampus on day 1 after trauma. CS peak was detected on day 3 in blood, the ipsilateral and contralateral hippocampus. Neuronal cell loss in the hippocampus was demonstrated bilaterally; in the ipsilateral hippocampus it started earlier than in the contralateral. Microglial activation was evident in the hippocampus bilaterally on day 7 after TBI. The duration of immediate seizures correlated with CS elevation, levels of IL-1β and neuronal loss in the hippocampus. The data suggest potential association of immediate post-traumatic seizures with CS-dependent neuroinflammation-mediated distant hippocampal damage.

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Deficits in pattern separation and dentate gyrus proliferation after rodent lateral fluid percussion injury

IBRO Neuroscience Reports ◽

10.1016/j.ibneur.2020.11.005 ◽

2021 ◽

Vol 10 ◽

pp. 31-41

Author(s):

Erika A. Correll ◽

Benjamin J. Ramser ◽

Maxon V. Knott ◽

Robert E. McCullumsmith ◽

Jennifer L. McGuire ◽

...

Keyword(s):

Dentate Gyrus ◽

Pattern Separation ◽

Fluid Percussion ◽

Fluid Percussion Injury ◽

Lateral Fluid Percussion

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Environmental enrichment increases progenitor cell survival in the dentate gyrus following lateral fluid percussion injury

Molecular Brain Research ◽

10.1016/j.molbrainres.2005.08.011 ◽

2005 ◽

Vol 141 (2) ◽

pp. 138-150 ◽

Cited By ~ 38

Author(s):

Lindsey J. Gaulke ◽

Philip J. Horner ◽

Andrew J. Fink ◽

Courtney L. McNamara ◽

Ramona R. Hicks

Keyword(s):

Dentate Gyrus ◽

Cell Survival ◽

Progenitor Cell ◽

Environmental Enrichment ◽

Fluid Percussion ◽

Fluid Percussion Injury ◽

Lateral Fluid Percussion

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Rat Neonatal Immune Challenge Alters Adult Responses to Cerebral Ischaemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9600206 ◽

2005 ◽

Vol 26 (4) ◽

pp. 456-467 ◽

Cited By ~ 35

Author(s):

Sarah J Spencer ◽

Roland N Auer ◽

Quentin J Pittman

Keyword(s):

Cerebral Ischaemia ◽

Early Period ◽

Neuronal Cell ◽

Cell Loss ◽

Central Nucleus ◽

Immune Challenge ◽

Vessel Occlusion ◽

Neuronal Cell Loss ◽

Temperature Responses ◽

Behavioural Deficits

Infection, inflammation, and hyperthermia associated with cerebral ischaemia are known to contribute to enhanced neuronal cell loss and more severe behavioural deficits. Because neonatal exposure to an immune challenge has been shown to alter the severity of inflammatory and febrile responses to a further immune challenge experienced in adulthood, we hypothesised that this could also alter temperature responses and neuronal survival after ischaemia. Thus, male Sprague–Dawley rats were treated at postnatal day 14 with a single injection of the bacterial endotoxin lipopolysaccharide (LPS) and were examined as adults for temperature changes, behavioural deficits, and neuronal cell loss associated with global cerebral ischaemia after a two-vessel occlusion (2 VO). Neonatally LPS-treated rats showed behavioural differences in a novel object exploration paradigm, as well as altered temperature responses to the 2 VO compared with neonatally salinetreated controls. Interestingly, these neonatally LPS-treated rats also showed increased cell loss in the central nucleus of the amygdala, a region that is important in the processing of emotional responses, but that is not usually examined in animal models of cerebral ischaemia. No differences were seen in the CA1, CA3, or dentate gyrus regions of the hippocampus. This work shows the importance of examining brain regions other than the hippocampus in association with global ischaemia. We also highlight the importance of the early period of development in programming an animal's ability to deal with injury such as cerebral ischaemia in adulthood.

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Surgical treatment of limbic epilepsy associated with extrahippocampal lesions: the problem of dual pathology

Journal of Neurosurgery ◽

10.3171/jns.1991.75.3.0364 ◽

1991 ◽

Vol 75 (3) ◽

pp. 364-370 ◽

Cited By ~ 192

Author(s):

Michel F. Lévesque ◽

Nobukazu Nakasato ◽

Harry V. Vinters ◽

Thomas L. Babb

Keyword(s):

Surgical Treatment ◽

Intractable Epilepsy ◽

Neuronal Cell ◽

Cell Loss ◽

Control Group ◽

Hippocampal Damage ◽

Content Type ◽

Dual Pathology ◽

Hippocampal Cell ◽

Fine Print

✓ The authors present their review of 178 patients who underwent en bloc temporal lobectomies as surgical treatment for intractable epilepsy. Hippocampal cell density was quantitatively analyzed and the histology of the anterior temporal lobe was reviewed. Fifty-four patients (30.3%) had evidence of extrahippocampal lesions in addition to neuronal cell loss within the hippocampus (the dual pathology group). The pattern of cell loss was analyzed in the remaining 124 cases (69.7%) with no extrahippocampal pathology, and compared with that of the dual pathology group and a control group of four nonepileptic patients. Hippocampal cell loss was found in almost all epileptic patients compared to the control group. Severe cell loss greater than 30% of control values was found in 88.7% of patients without extrahippocampal lesions, but in only 51.8% of patients with dual pathology. The difference between these two groups was statistically significant (p < 0.001). In the dual pathology group, lesions of different pathology had a significant relationship with the degree of hippocampal cell loss: all 12 patients with glioma had mild cell loss, whereas all 13 patients with heterotopia were associated with severe cell loss. Severity of hippocampal cell loss was also analyzed in relation to seizure history: a prior severe head injury was associated with severe cell loss. Other factors such as seizure duration, secondary generalization, or family history of seizures were not associated with hippocampal damage. Dual pathology may produce a combination of neocortical and temporolimbic epilepsies that warrants a precise definition of the true epileptogenic area prior to surgical treatment.

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Faculty Opinions recommendation of A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14259.471759 ◽

2006 ◽

Author(s):

Susan Herman

Keyword(s):

Brain Injury ◽

Posttraumatic Epilepsy ◽

Fluid Percussion ◽

Lateral Fluid Percussion

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Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats

Scientific Reports ◽

10.1038/s41598-020-79374-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Johanna Habermeyer ◽

Janina Boyken ◽

Julia Harrer ◽

Fabio Canneva ◽

Veronika Ratz ◽

...

Keyword(s):

Neuronal Cell ◽

Cell Loss ◽

Repeated Administration ◽

Perineuronal Net ◽

Treatment Groups ◽

Long Time ◽

Clinical Consequences ◽

Molecular Weight Fractions ◽

Clinical Mri ◽

Pathway Deregulation

AbstractGadolinium based contrast agents (GBCAs) are widely used in clinical MRI since the mid-1980s. Recently, concerns have been raised that trace amounts of Gadolinium (Gd), detected in brains even long time after GBCA application, may cause yet unrecognized clinical consequences. We therefore assessed the behavioral phenotype, neuro-histopathology, and Gd localization after repeated administration of linear (gadodiamide) or macrocyclic (gadobutrol) GBCA in rats. While most behavioral tests revealed no difference between treatment groups, we observed a transient and reversible decrease of the startle reflex after gadodiamide application. Residual Gd in the lateral cerebellar nucleus was neither associated with a general gene expression pathway deregulation nor with neuronal cell loss, but in gadodiamide-treated rats Gd was associated with the perineuronal net protein aggrecan and segregated to high molecular weight fractions. Our behavioral finding together with Gd distribution and speciation support a substance class difference for Gd presence in the brain after GBCA application.

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