Neuronal injury and loss after traumatic brain injury: time course and regional variability

Sato, Motoki; Chang, Edward F.; Igarashi, Takuji; Noble, Linda

doi:10.1016/s0006-8993(01)02905-5

Cited by 180 publications

(129 citation statements)

References 28 publications

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“…Early time points show FJ extending well into cell processes, while at later time points the FJ þ cells appear smaller than surrounding neurons, with retracted or absent processes. This is consistent with other descriptions of FJ staining after traumatic brain injury or excitotoxicity (Sato et al, 2001;Gilliams-Francis et al, 2003;Singleton and Povlishok, 2004). Since the initial description of FJ as a marker of neuron death, there have been only two reports of FJ staining nonneuronal cells in rat CNS injury models.…”

Section: Discussionsupporting

confidence: 90%

“…The mechanism of cell death is not indicated by these results, because FJ, like silver staining, marks cells dying from either apoptosis or necrosis (Sato et al, 2001). We did not detect labeled cells after hypoglycemic insult by using immunohistochemical probes of caspase and calpain pathways.…”

Section: Discussionmentioning

confidence: 89%

“…The data presented here show positive staining with FJ after a single 75 mins episode of moderate, hypoglycemia that did not cause loss of consciousness. Fluoro-Jade B has been used as a marker of neuron death in a variety of brain injury models including ischemia, traumatic brain injury, and excitotoxicity (Sato et al, 2001;Butler et al, 2002). A previous study using FJ to assess brain injury after hypoglycemic coma indicated that FJ labels neurons in the cortex, hippocampus, and subiculum after 30 mins of cerebral isoelectricity (Suh et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…The time points and experimental manipulations were based on our prior study with the following modifications: epinephrine, norepinephrine, glucagon, and corticosterone responses to equivalent mild hypoglycemia were compared between rats studied 48 h after a single episode of moderate hypoglycemia and control, pair-fasted rats. Immediately after blood sampling for hormone measurements was completed, these rats were euthanized and perfused for subsequent neuropathologic assessment using Fluoro-Jade B (FJ), a recently developed putative marker of neuron death Sato et al, 2001;Muñ oz et al, 2001). The second experiment characterized the time course of appearance of FJ and other injury markers after moderate hypoglycemia in rats that were not subjected to blood sampling for hormone measurements.…”

Section: Introductionmentioning

confidence: 99%

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Cortical Fluoro-Jade Staining and Blunted Adrenomedullary Response to Hypoglycemia after Noncoma Hypoglycemia in Rats

Tkacs

Pan

Raghupathi

et al. 2005

J Cereb Blood Flow Metab

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Intensive insulin therapy in patients with type 1 diabetes mellitus reduces long-term complications; however, intensive therapy is also associated with a three-fold increase in hypoglycemic episodes. The present study in conscious rats characterizes the physiologic and neuropathologic consequences of a single episode of moderate hypoglycemia. In this model, intravenous insulin is used to reduce plasma glucose to 30 to 35 mg/dL for 75 mins. This single hypoglycemic insult acutely induces hypoglycemia-associated autonomic failure (HAAF), with epinephrine responses to hypoglycemia reduced more than 36% from control. Neuropathology after this insult includes the appearance of dying cells, assessed with the marker Fluoro-jade B (FJ). After hypoglycemic insult, FJ þ cells were consistently seen in subdivisions of the medial prefrontal cortex, the orbital cortex, and the piriform cortex. There was a significant correlation between depth of hypoglycemia and number of FJ þ cells, suggesting that there is a critical threshold below which vulnerable cells begin to die. These data suggest that there is a population of cells that are vulnerable to moderate levels of hypoglycemia commonly experienced by patients with insulin-treated diabetes. These cells, which may be neurons, are primarily found in cortical regions implicated in visceral perception and autonomic control, raising the possibility that their loss contributes to clinically reported deficits in autonomic and perceptual responses to hypoglycemia.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cortical Fluoro-Jade Staining and Blunted Adrenomedullary Response to Hypoglycemia after Noncoma Hypoglycemia in Rats

Tkacs

Pan

Raghupathi

et al. 2005

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…Brain injury consistently produced an acute apnea in all animals (28 ± 15 s), and resulted in marked tissue damage observed in the ipsilateral cortex, white matter tracts and hippocampus using cresyl violet-stained sections (data not shown) as has been previously shown in numerous reports using the FP brain injury model (Hicks et al, 1996;Sato et al, 2001). Five animals died in the immediate post-injury period, producing an injury mortality of 18%, consistent with previous reports using the lateral FP brain injury model of moderate severity (Saatman et al, 1997).…”

Section: Resultssupporting

confidence: 73%

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Marklund

Fulp

Shimizu

et al. 2006

Experimental Neurology

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Axons show a poor regenerative capacity following traumatic central nervous system (CNS) injury, partly due to the expression of inhibitors of axonal outgrowth, of which Nogo-A is considered the most important. We evaluated the acute expression of Nogo-A, the Nogo-66 receptor (NgR) and the novel small proline-rich repeat protein 1A (SPRR1A, previously undetected in brain), following experimental lateral fluid percussion (FP) brain injury in rats. Immunofluorescence with antibodies against Nogo-A, NgR and SPRR1A was combined with antibodies against the neuronal markers NeuN and microtubule-associated protein (MAP)-2 and the oligodendrocyte marker RIP, while Western blot analysis was performed for Nogo-A and NgR. Brain injury produced a significant increase in Nogo-A expression in injured cortex, ipsilateral external capsule and reticular thalamus from days 1-7 post-injury (P < 0.05) compared to controls. Increased expression of Nogo-A was observed in both RIP-and NeuN positive (+) cells in the ipsilateral cortex, in NeuN (+) cells in the CA3 region of the hippocampus and reticular thalamus and in RIP (+) cells in white matter tracts. Alterations in NgR expression were not observed following traumatic brain injury (TBI). Brain injury increased the extent of SPRR1A expression in the ipsilateral cortex and the CA3 at all post-injury time-points in NeuN (+) cells. The marked increases in Nogo-A and SPRR1A in several important brain regions suggest that although inhibitors of axonal growth may be upregulated, the injured brain is also capable of expressing proteins promoting axonal outgrowth following TBI. KeywordsNogo-A; Nogo-66 receptor; Small proline-rich repeat protein 1A (SPRR1A); Traumatic brain injury; Oligodendrocytes

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Inhibitory neuronal changes following a mixed diffuse‐focal model of traumatic brain injury

Carron

Sun

Shultz

et al. 2019

J of Comparative Neurology

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Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range of chronic neurological deficits. However, how TBI affects different interneurons, and how this relates to behavioral abnormalities, remains poorly understood. This study examined the effects of a mixed diffuse‐focal model of TBI, the lateral fluid percussion injury (LFPI), on interneurons, 8 weeks post‐TBI in rats. Brains were labeled with antibodies against calbindin, parvalbumin, calretinin, neuropeptide Y, and somatostatin, and the number of interneurons were assessed in the cortex and hippocampus following LFPI. LFPI caused a reduction in the numbers of interneurons mediating both perisomatic and dendritic inhibition in the somatosensory cortex. In hippocampus, there were heterogenous changes in the number of interneurons while motor cortex, showed no obvious loss in any of the subsets of interneurons after TBI. In parallel to the investigations of changes in the number of interneurons, we also investigated the long‐term behavioral consequences of LFPI. Behaviorally, rats given an LFPI displayed transient reduction in performance in motor tasks and were significantly impaired in reversal learning in the water maze task post‐TBI. We also report here progressive neurodegeneration in cortex and hippocampus indicated by Fluoro‐Jade C in the different brain areas examined after injury. Our findings suggest differential vulnerability of inhibitory neurons to LFPI in the different brain areas examined after injury. These data will aid in evaluation of new treatments for TBI and help target specific neuronal subtypes as a function of injury time and type.

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Neuronal injury and loss after traumatic brain injury: time course and regional variability

Cited by 180 publications

References 28 publications

Cortical Fluoro-Jade Staining and Blunted Adrenomedullary Response to Hypoglycemia after Noncoma Hypoglycemia in Rats

Cortical Fluoro-Jade Staining and Blunted Adrenomedullary Response to Hypoglycemia after Noncoma Hypoglycemia in Rats

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Inhibitory neuronal changes following a mixed diffuse‐focal model of traumatic brain injury

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