Controlled Cortical Impact Injury Model

Dixon, C. Edward; Kline, Anthony E.

doi:10.1007/978-1-60327-185-1_33

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…First developed by Lighthall (1988), this model often utilizes an electronically controlled pneumatic impactor to apply a focal contusion injury to the brain surface through a craniotomy (Dixon et al, 1991; Scheff et al, 1997; Hall et al, 2005, 2008; Saatman et al, 2006; Dixon and Kline, 2009). Injury severity is primarily managed by adjusting the depth of tissue compression, but other external injury parameters can also be controlled with precision (i.e., impact depth and velocity, impactor shape and size, and number of craniotomies).…”

Section: Animal Models Of Ptementioning

confidence: 99%

Neural circuit mechanisms of post–traumatic epilepsy

Hunt¹,

Boychuk²,

Smith³

2013

Front. Cell. Neurosci.

146

134

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Traumatic brain injury (TBI) greatly increases the risk for a number of mental health problems and is one of the most common causes of medically intractable epilepsy in humans. Several models of TBI have been developed to investigate the relationship between trauma, seizures, and epilepsy-related changes in neural circuit function. These studies have shown that the brain initiates immediate neuronal and glial responses following an injury, usually leading to significant cell loss in areas of the injured brain. Over time, long-term changes in the organization of neural circuits, particularly in neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and increased risk for spontaneous seizures. These include alterations to inhibitory interneurons and formation of new, excessive recurrent excitatory synaptic connectivity. Here, we review in vivo models of TBI as well as key cellular mechanisms of synaptic reorganization associated with post-traumatic epilepsy (PTE). The potential role of inflammation and increased blood–brain barrier permeability in the pathophysiology of PTE is also discussed. A better understanding of mechanisms that promote the generation of epileptic activity versus those that promote compensatory brain repair and functional recovery should aid development of successful new therapies for PTE.

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Section: Animal Models Of Ptementioning

confidence: 99%

Neural circuit mechanisms of post–traumatic epilepsy

Hunt¹,

Boychuk²,

Smith³

2013

Front. Cell. Neurosci.

146

134

View full text Add to dashboard Cite

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Evaluation of a Combined Therapeutic Regimen of 8-OH-DPAT and Environmental Enrichment after Experimental Traumatic Brain Injury

Kline

McAloon²,

Henderson³

et al. 2010

Journal of Neurotrauma

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126

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When provided individually, both the serotonin (5-HT 1A )-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and environmental enrichment (EE) enhance behavioral outcome and reduce histopathology after experimental traumatic brain injury (TBI). The aim of this study was to determine whether combining these therapies would yield greater benefit than either used alone. Anesthetized adult male rats received a cortical impact or sham injury and then were randomly assigned to enriched or standard (STD) housing, where either 8-OH-DPAT (0.1 mg/kg) or vehicle (1.0 mL/kg) was administered intraperitoneally once daily for 3 weeks. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. CA1/ CA3 neurons and choline acetyltransferase-positive (ChAT þ ) medial septal cells were quantified at 3 weeks. 8-OH-DPAT and EE attenuated CA3 and ChAT þ cell loss. Both therapies also enhanced motor recovery, acquisition of spatial learning, and memory retention, as verified by reduced times to traverse the beam and to locate an escape platform in the water maze, and a greater percentage of time spent searching in the target quadrant during a probe trial in the TBI þ STD þ 8-OH-DPAT, TBI þ EE þ 8-OH-DPAT, and TBI þ EE þ vehicle groups versus the TBI þ STD þ vehicle group ( p 0.0016). No statistical distinctions were revealed between the TBI þ EE þ 8-OH-DPAT and TBI þ EE þ vehicle groups in functional outcome or CA1/CA3 cell survival, but there were significantly more ChAT þ cells in the former ( p ¼ 0.003). These data suggest that a combined therapeutic regimen of 8-OH-DPAT and EE reduces TBI-induced ChAT þ cell loss, but does not enhance hippocampal cell survival or neurobehavioral performance beyond that of either treatment alone. The findings underscore the complexity of combinational therapies and of elucidating potential targets for TBI.

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Evolution of neuronal and astroglial disruption in the peri-contusional cortex of mice revealed by in vivo two-photon imaging

Sword

Masuda

Croom

et al. 2013

Brain

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In traumatic brain injury mechanical forces applied to the cranium and brain cause irreversible primary neuronal and astroglial damage associated with terminal dendritic beading and spine loss representing acute damage to synaptic circuitry. Oedema develops quickly after trauma, raising intracranial pressure that results in a decrease of blood flow and consequently in cerebral ischaemia, which can cause secondary injury in the peri-contusional cortex. Spreading depolarizations have also been shown to occur after traumatic brain injury in humans and in animal models and are thought to accelerate and exacerbate secondary tissue injury in at-risk cortical territory. Yet, the mechanisms of acute secondary injury to fine synaptic circuitry within the peri-contusional cortex after mild traumatic brain injury remain unknown. A mild focal cortical contusion model in adult mouse sensory-motor cortex was implemented by the controlled cortical impact injury device. In vivo two-photon microscopy in the peri-contusional cortex was used to monitor via optical window yellow fluorescent protein expressing neurons, enhanced green fluorescent protein expressing astrocytes and capillary blood flow. Dendritic beading in the peri-contusional cortex developed slowly and the loss of capillary blood flow preceded terminal dendritic injury. Astrocytes were swollen indicating oedema and remained swollen during the next 24 h throughout the imaging session. There were no recurrent spontaneous spreading depolarizations in this mild traumatic brain injury model; however, when spreading depolarizations were repeatedly induced outside the peri-contusional cortex by pressure-injecting KCl, dendrites undergo rapid beading and recovery coinciding with passage of spreading depolarizations, as was confirmed with electrophysiological recordings in the vicinity of imaged dendrites. Yet, accumulating metabolic stress resulting from as few as four rounds of spreading depolarization significantly added to the fraction of beaded dendrites that were incapable to recover during repolarization, thus facilitating terminal injury. In contrast, similarly induced four rounds of spreading depolarization in another set of control healthy mice caused no accumulating dendritic injury as dendrites fully recovered from beading during repolarization. Taken together, our data suggest that in the mild traumatic brain injury the acute dendritic injury in the peri-contusional cortex is gated by the decline in the local blood flow, most probably as a result of developing oedema. Furthermore, spreading depolarization is a specific mechanism that could accelerate injury to synaptic circuitry in the metabolically compromised peri-contusional cortex, worsening secondary damage following traumatic brain injury.

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Controlled Cortical Impact Injury Model

Cited by 3 publications

References 29 publications

Neural circuit mechanisms of post–traumatic epilepsy

Neural circuit mechanisms of post–traumatic epilepsy

Evaluation of a Combined Therapeutic Regimen of 8-OH-DPAT and Environmental Enrichment after Experimental Traumatic Brain Injury

Evolution of neuronal and astroglial disruption in the peri-contusional cortex of mice revealed by in vivo two-photon imaging

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