The possible role of hypoxia in the formation of axonal bulbs.

Kaur, B; Rutty, Guy N.; Timperley, W. R.

doi:10.1136/jcp.52.3.203

Cited by 62 publications

(35 citation statements)

References 20 publications

(19 reference statements)

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“…Harrington et al [2] demonstrated that 11 of 20 cases with histological changes of hypoxia without head injury showed positive APP staining and survival times from 1 h to 3 months. Kaur et al [14] reported that 12 of 25 cases of hypoxia without head injury showed positive APP staining and survival times from a few hours to 68 days. However, specific staining patterns of the labeled axons were not mentioned in their investigations [2,14].…”

Section: Discussionmentioning

confidence: 99%

“…These axonal bulbs form usually in the presence of both intracranial and systemic pathology, such as cerebral infarction/ hemorrhage, meningitis, bronchopneumonia, hypoglycemia, and drug intoxication as well as in cases of ventilator support [5,7,[12][13][14][15]. In particular, hypoxia and ischemic brain damage without head injury show the formation of axonal bulbs.…”

Section: Introductionmentioning

confidence: 99%

“…Posttraumatic edema and cerebral and cerebellar herniation secondary to head injury may also cause axonal bulbs. Therefore, it is necessary to distinguish the detection of APP after traumatic axonal injury from other axonal injuries [7,[12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury

et al. 2015

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Immunostaining for beta-amyloid precursor protein (APP) is recognized as an effective tool for detecting traumatic axonal injury, but it also detects axonal injury due to ischemic or other metabolic causes. Previously, we reported two different patterns of APP staining: labeled axons oriented along with white matter bundles (pattern 1) and labeled axons scattered irregularly (pattern 2) (Hayashi et al. (Leg Med (Tokyo) 11:S171-173, 2009). In this study, we investigated whether these two patterns are consistent with patterns of trauma and hypoxic brain damage, respectively. Sections of the corpus callosum from 44 cases of blunt head injury and equivalent control tissue were immunostained for APP. APP was detected in injured axons such as axonal bulbs and varicose axons in 24 of the 44 cases of head injuries that also survived for three or more hours after injury. In 21 of the 24 APP-positive cases, pattern 1 alone was observed in 14 cases, pattern 2 alone was not observed in any cases, and both patterns 1 and 2 were detected in 7 cases. APP-labeled injured axons were detected in 3 of the 44 control cases, all of which were pattern 2. These results suggest that pattern 1 indicates traumatic axonal injury, while pattern 2 results from hypoxic insult. These patterns may be useful to differentiate between traumatic and nontraumatic axonal injuries.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury

et al. 2015

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“…These findings further emphasize the inter-and intrapatient variability that has been previously detailed in other clinicopathological studies of fatal malaria. [2][3][4][5] Recent literature has raised the possibility that hypoxia, 26 raised intracranial pressure, 26 -29 and hypoglycemia 30 can cause AI. We found no association between AI and intracranial pressure or hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

Axonal Injury in Cerebral Malaria

Medana¹,

Day²,

Hien³

et al. 2002

The American Journal of Pathology

155

130

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Impairment of consciousness and other signs of cerebral dysfunction are common complications of severe Plasmodium falciparum malaria. Although the majority of patients make a complete recovery a significant minority, particularly children, have sequelae. The pathological process by which P. falciparum malaria induces severe but usually reversible neurological complications has not been elucidated. Impairment of transport within nerve fibers could induce neurological dysfunction and may have the potential either to resolve or to progress to irreversible damage. ␤-amyloid precursor protein (␤-APP) immunocytochemistry, quantified using digital image analysis, was used to detect defects in axonal transport in brain sections from 54 Vietnamese cases with P. falciparum malaria. The frequency and extent of ␤-APP staining were more severe in patients with cerebral malaria than in those with no clinical cerebral involvement. ␤-APP staining was often associated with hemorrhages and areas of demyelination, suggesting that multiple processes may be involved in neuronal injury. The age of focal axonal damage, as determined by the extent of the associated microglial response, varied considerably within tissue sections from individual patients. These findings suggest that axons are vulnerable to a broad range of cerebral insults that occur during P. falciparum malaria infection. Disruption in axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria. Cerebral malaria (CM) is a diffuse, potentially reversible, encephalopathy, caused by infection with the protozoan parasite Plasmodium falciparum. CM presents clinically with convulsions and coma, and carries 15 to 20% mortality. The malaria parasite invades and develops within erythrocytes that sequester in the cerebral microvasculature and other vital organs by adhesion to specific endothelial receptors. 1,2 The pathophysiological consequences of severe malaria infection have not been satisfactorily resolved. In particular it is not known how parasitized red blood cells, which remain within the vascular space, influence parenchymal brain function to induce coma and death. Histopathological studies reveal a variety of neurological abnormalities including chromatolysis, neuronophagia, and decreased glial cell numbers. [2][3][4][5]

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“…10,11 It remains unclear whether TAI in white matter is entirely the result of primary injury or if commonly occurring secondary insults (such as increased intracranial pressure (ICP), hypoxia, or hypotension) after TBI can influence the extent and severity of axonal injury. [12][13][14][15] Reduction and avoidance of elevations in ICP continue to be the mainstays of treatment patients with for severe TBI. 10,11 Although there is evidence that sustained elevations in ICP > 20 mm Hg after severe TBI are associated with poor outcome, efficacy of threshold-targeted interventions has not been thoroughly established.…”

Section: Introductionmentioning

confidence: 99%

Decompressive Craniectomy Reduces White Matter Injury after Controlled Cortical Impact in Mice

Friess

Lapidus

Brody

2015

Journal of Neurotrauma

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Reduction and avoidance of increases in intracranial pressure (ICP) after severe traumatic brain injury (TBI) continue to be the mainstays of treatment. Traumatic axonal injury is a major contributor to morbidity after TBI, but it remains unclear whether elevations in ICP influence axonal injury. Here we tested the hypothesis that reduction in elevations in ICP after experimental TBI would result in decreased axonal injury and white matter atrophy in mice. Six-week-old male mice (C57BL/6J) underwent either moderate controlled cortical impact (CCI) (n = 48) or Sham surgery (Sham, n = 12). Immediately after CCI, injured animals were randomized to a loose fitting plastic cap (Open) or replacement of the previously removed bone flap (Closed). Elevated ICP was observed in Closed animals compared with Open and Sham at 15 min (21.4 -4.2 vs. 12.3 -2.9 and 8.8 -1.8 mm Hg, p < 0.0001) and 1 day (17.8 -3.7 vs. 10.6 -2.0 and 8.9 -1.9 mm Hg, p < 0.0001) after injury. Beta amyloid precursor protein staining in the corpus callosum and ipsilateral external capsule revealed reduced axonal swellings and bulbs in Open compared with Closed animals (32% decrease, p < 0.01 and 40% decrease, p < 0.001 at 1 and 7 days post-injury, respectively). Open animals were also found to have decreased neurofilament-200 stained axonal swellings at 7 days post-injury compared with Open animals (32% decrease, p < 0.001). At 4 weeks post-injury, Open animals had an 18% reduction in white matter volume compared with 34% in Closed animals ( p < 0.01). Thus, our results indicate that CCI with decompressive craniectomy was associated with reductions in ICP and reduced pericontusional axonal injury and white matter atrophy. If similar in humans, therapeutic interventions that ameliorate intracranial hypertension may positively influence white matter injury severity.

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The possible role of hypoxia in the formation of axonal bulbs.

Cited by 62 publications

References 20 publications

Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury

Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury

Axonal Injury in Cerebral Malaria

Decompressive Craniectomy Reduces White Matter Injury after Controlled Cortical Impact in Mice

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