gliosis

Summary

Summary: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.

Top Publications

  1. Burda J, Sofroniew M. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron. 2014;81:229-48 pubmed publisher
    ..In some cases, considerable information is available, in others, comparatively little, as examined and reviewed here. ..
  2. Budde M, Janes L, Gold E, Turtzo L, Frank J. The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections. Brain. 2011;134:2248-60 pubmed publisher
    ..62, P?=?0.04) with the coherent organization of reactive astrocytes (i.e. gliosis) and was not attributed to axons. By comparison, a decrease in white matter anisotropy (P?<?0...
  3. do Nascimento A, Dos Santos N, Campos Pelágio F, Aparecida Teixeira S, de Moraes Ferrari E, Langone F. Neuronal degeneration and gliosis time-course in the mouse hippocampal formation after pilocarpine-induced status epilepticus. Brain Res. 2012;1470:98-110 pubmed publisher
    ..of human epilepsy and has been related with extensive loss of hippocampal pyramidal and dentate hilar neurons and gliosis. Many characteristics of TLE are reproduced in the pilocarpine model of epilepsy in mice...
  4. Xue W, Cojocaru R, Dudley V, Brooks M, Swaroop A, Sarthy V. Ciliary neurotrophic factor induces genes associated with inflammation and gliosis in the retina: a gene profiling study of flow-sorted, Müller cells. PLoS ONE. 2011;6:e20326 pubmed publisher
    ..We have, therefore, examined gene expression dynamics of purified Müller (glial) cells exposed to CNTF in vivo...
  5. Granado N, Lastres Becker I, Ares Santos S, Oliva I, Martin E, Cuadrado A, et al. Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum. Glia. 2011;59:1850-63 pubmed publisher
    Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity...
  6. Takahashi H, Kanesaki H, Igarashi T, Kameya S, Yamaki K, Mizota A, et al. Reactive gliosis of astrocytes and Müller glial cells in retina of POMGnT1-deficient mice. Mol Cell Neurosci. 2011;47:119-30 pubmed publisher
    ..Our results suggest that altered glycosylation of alpha-DG may be responsible for the reactive gliosis and reticular fibrosis in the retina, and the subsequent developments of retinal dysplasia, abnormal ERGs, and ..
  7. Sukumari Ramesh S, Alleyne C, Dhandapani K. Astrocyte-specific expression of survivin after intracerebral hemorrhage in mice: a possible role in reactive gliosis?. J Neurotrauma. 2012;29:2798-804 pubmed publisher
    ..Together, these data suggest a potentially novel role for survivin in functionally promoting astrocytic proliferation after ICH...
  8. Skripuletz T, Hackstette D, Bauer K, Gudi V, Pul R, Voss E, et al. Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain. 2013;136:147-67 pubmed publisher
    ..This is of great importance to understanding regenerative processes in demyelinating diseases such as multiple sclerosis...
  9. Devinsky O, Vezzani A, Najjar S, de Lanerolle N, Rogawski M. Glia and epilepsy: excitability and inflammation. Trends Neurosci. 2013;36:174-84 pubmed publisher
    ..This review critically evaluates the role of glia-induced hyperexcitability and inflammation in epilepsy...

More Information

Publications62

  1. Hayes D, Deeny M, Shaner C, Nixon K. Determining the threshold for alcohol-induced brain damage: new evidence with gliosis markers. Alcohol Clin Exp Res. 2013;37:425-34 pubmed publisher
    ..Little is known about the threshold of the damaging effects of alcohol. Therefore, these experiments sought to determine a threshold for brain damage using various markers of neurodegeneration...
  2. Goodrich G, Kabakov A, Hameed M, Dhamne S, Rosenberg P, Rotenberg A. Ceftriaxone treatment after traumatic brain injury restores expression of the glutamate transporter, GLT-1, reduces regional gliosis, and reduces post-traumatic seizures in the rat. J Neurotrauma. 2013;30:1434-41 pubmed publisher
    ..001). We cautiously conclude that our data suggest a potential role for ceftriaxone in treatment of epileptogenic TBI...
  3. Bianco M, Cirillo G, Petrosino V, Marcello L, Soleti A, Merizzi G, et al. Neuropathic pain and reactive gliosis are reversed by dialdehydic compound in neuropathic pain rat models. Neurosci Lett. 2012;530:85-90 pubmed publisher
    ..These data prompt to hypothesize a potential role of dialdehydes as analgesic agent in chronic neuropathic pain and a possible role as anti-gliotic molecules...
  4. Ohk T, Yoo K, Park S, Shin B, Kim I, Park J, et al. Neuronal damage using fluoro-jade B histofluorescence and gliosis in the striatum after various durations of transient cerebral ischemia in gerbils. Neurochem Res. 2012;37:826-34 pubmed publisher
    ..In addition, we examined gliosis of astrocytes and microglia using anti-glial fibrillary acidic protein (GFAP) and anti- ionized calcium-binding ..
  5. Yang L, Fang J, Wang W, Chen R, Shen C. Transplantation of Schwann cells differentiated from adipose-derived stem cells modifies reactive gliosis after contusion brain injury in rats. J Int Med Res. 2011;39:1344-57 pubmed
    ..of rats could promote functional improvement after contusion brain injury, with a focus on the effect on reactive gliosis. ADSCs were isolated and expanded from groin adipose tissue of Sprague-Dawley rats and then differentiated into ..
  6. Lively S, Moxon Emre I, Schlichter L. SC1/hevin and reactive gliosis after transient ischemic stroke in young and aged rats. J Neuropathol Exp Neurol. 2011;70:913-29 pubmed publisher
    ..Their differing expression of inflammation-related and putatively protective molecules suggests different roles for starburst and classic reactive astrocytes in the early glial responses to ischemia...
  7. Serrano Pozo A, Mielke M, Gomez Isla T, Betensky R, Growdon J, Frosch M, et al. Reactive glia not only associates with plaques but also parallels tangles in Alzheimer's disease. Am J Pathol. 2011;179:1373-84 pubmed publisher
    ..They also suggest that reactive glia might contribute to the ongoing neurodegeneration...
  8. Siopi E, Cho A, Homsi S, Croci N, Plotkine M, Marchand Leroux C, et al. Minocycline restores sAPP? levels and reduces the late histopathological consequences of traumatic brain injury in mice. J Neurotrauma. 2011;28:2135-43 pubmed publisher
    ..p.) and at 3 and 9?h (45?mg/kg, i.p.) post-TBI. The levels of sAPP?, the extent of brain atrophy, and reactive gliosis were evaluated by ELISA, cresyl violet, and immunolabeling of GFAP and CD11b, respectively...
  9. Little A, Miller D, Li S, Kashon M, O Callaghan J. Trimethyltin-induced neurotoxicity: gene expression pathway analysis, q-RT-PCR and immunoblotting reveal early effects associated with hippocampal damage and gliosis. Neurotoxicol Teratol. 2012;34:72-82 pubmed publisher
    ..These observations provide new insight into early events associated with neuronal degeneration and associated glial activation that may serve as the basis for discovery and development of biomarkers of neurotoxicity...
  10. López Rodríguez A, Mateos Vicente B, Romero Zerbo S, Rodriguez Rodriguez N, Bellini M, Rodriguez de Fonseca F, et al. Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors. Cereb Cortex. 2011;21:2046-55 pubmed publisher
    ..reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids...
  11. Prakash D, Gopinath K, Sudhandiran G. Fisetin enhances behavioral performances and attenuates reactive gliosis and inflammation during aluminum chloride-induced neurotoxicity. Neuromolecular Med. 2013;15:192-208 pubmed publisher
    ..Astrocyte, microglia activation (reactive gliosis), and associated inflammatory events play a decisive role in neurodegeneration and may represent a target for ..
  12. Cowley T, González Reyes R, Richardson J, Virley D, Upton N, Lynch M. The age-related gliosis and accompanying deficit in spatial learning are unaffected by dimebon. Neurochem Res. 2013;38:1190-5 pubmed publisher
    ..We conclude that, despite its cognitive enhancing effects in some models, dimebon failed to modulate the deficit in spatial learning in aged rats and the evidence suggests that the drug does not possess anti-inflammatory properties...
  13. Ji M, Miao Y, Dong L, Chen J, Mo X, Jiang S, et al. Group I mGluR-mediated inhibition of Kir channels contributes to retinal Müller cell gliosis in a rat chronic ocular hypertension model. J Neurosci. 2012;32:12744-55 pubmed publisher
    Müller cell gliosis, which is characterized by upregulated expression of glial fibrillary acidic protein (GFAP), is a universal response in many retinal pathological conditions...
  14. Zgavc T, Ceulemans A, Hachimi Idrissi S, Kooijman R, Sarre S, Michotte Y. The neuroprotective effect of post ischemic brief mild hypothermic treatment correlates with apoptosis, but not with gliosis in endothelin-1 treated rats. BMC Neurosci. 2012;13:105 pubmed publisher
    ..Apoptosis was determined using caspase-3 immunohistochemistry, phagocytic cells were visualized by CD-68 expression and astrogliosis was studied by glial fibrillary acidic protein (GFAP) staining...
  15. Tribouillard Tanvier D, Race B, Striebel J, Carroll J, Phillips K, Chesebro B. Early cytokine elevation, PrPres deposition, and gliosis in mouse scrapie: no effect on disease by deletion of cytokine genes IL-12p40 and IL-12p35. J Virol. 2012;86:10377-83 pubmed publisher
    ..The goal of our current research was to determine the relationship between cytokine responses, gliosis, and neuropathology during prion disease...
  16. Ryu M, Liu Y, Zhong X, Du J, Peterson N, Kong G, et al. Oncogenic Kras expression in postmitotic neurons leads to S100A8-S100A9 protein overexpression and gliosis. J Biol Chem. 2012;287:22948-58 pubmed publisher
    Previous studies suggest that up-regulation of Ras signaling in neurons promotes gliosis and astrocytoma formation in a cell nonautonomous manner. However, the underlying mechanisms remain unknown...
  17. Bagheri M, Roghani M, Joghataei M, Mohseni S. Genistein inhibits aggregation of exogenous amyloid-beta???? and alleviates astrogliosis in the hippocampus of rats. Brain Res. 2012;1429:145-54 pubmed publisher
    ..0001), CA1 (P=0.03), and CA3 (P=0.002); an increased number of iNOS-expressing cells (P=0.01) and gliosis. Genistein given to rats by gavage 1h before injection of A?(1-40) inhibited the formation of A?(1-40) positive ..
  18. Zamanian J, Xu L, Foo L, Nouri N, Zhou L, Giffard R, et al. Genomic analysis of reactive astrogliosis. J Neurosci. 2012;32:6391-410 pubmed publisher
    ..We find reactive gliosis consists of a rapid, but quickly attenuated, induction of gene expression after insult and identify induced Lcn2 ..
  19. Arevalo M, Santos Galindo M, Acaz Fonseca E, Azcoitia I, Garcia Segura L. Gonadal hormones and the control of reactive gliosis. Horm Behav. 2013;63:216-21 pubmed publisher
    ..This phenomenon is known as reactive gliosis. Activation of astrocytes and microglia after acute neural insults, such as stroke or traumatic CNS injury, is ..
  20. Hu L, Luo Y, Zhang J, Lei X, Shen J, Wu Y, et al. EPO reduces reactive gliosis and stimulates neurotrophin expression in Muller cells. Front Biosci (Elite Ed). 2011;3:1541-55 pubmed
    ..Exogenous EPO exerts neuroprotective and neurotrophic functions by attenuating reactive gliosis and promoting neurotrophic factors in Muller cells in diabetic retina...
  21. Lee J, Ahn J, Lee D, Yan B, Park J, Kim I, et al. Neuronal damage and gliosis in the somatosensory cortex induced by various durations of transient cerebral ischemia in gerbils. Brain Res. 2013;1510:78-88 pubmed publisher
    ..In addition, we immunohistochemically examined gliosis of astrocytes and microglia using anti-glial fibrillary acidic protein (GFAP) and anti-ionized calcium-binding ..
  22. Porritt M, Andersson H, Hou L, Nilsson A, Pekna M, Pekny M, et al. Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane. PLoS ONE. 2012;7:e41090 pubmed publisher
    ..The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage...
  23. Dinet V, Bruban J, Chalour N, Maoui A, An N, Jonet L, et al. Distinct effects of inflammation on gliosis, osmohomeostasis, and vascular integrity during amyloid beta-induced retinal degeneration. Aging Cell. 2012;11:683-93 pubmed publisher
    ..RMG cell gliosis (upregulation of GFAP, vimentin, and nestin) on day 1 postinjection and a proinflammatory phenotype were the ..
  24. Thaler J, Yi C, Schur E, Guyenet S, Hwang B, Dietrich M, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122:153-62 pubmed publisher
    ..Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within ..
  25. Ceulemans A, Zgavc T, Kooijman R, Hachimi Idrissi S, Sarre S, Michotte Y. Mild hypothermia causes differential, time-dependent changes in cytokine expression and gliosis following endothelin-1-induced transient focal cerebral ischemia. J Neuroinflammation. 2011;8:60 pubmed publisher
    ..This study is the first to investigate whether this neuroprotection occurs through modulation of the neuroinflammatory response after stroke in a time-dependent manner...
  26. Fellner L, Jellinger K, Wenning G, Stefanova N. Glial dysfunction in the pathogenesis of ?-synucleinopathies: emerging concepts. Acta Neuropathol. 2011;121:675-93 pubmed publisher
    ..Finally, major therapeutic strategies targeting glial pathology in ?-synucleinopathies as well as current pitfalls for disease-modification in clinical trials are discussed...
  27. Li T, Lytle N, Lan J, Sandau U, Boison D. Local disruption of glial adenosine homeostasis in mice associates with focal electrographic seizures: a first step in epileptogenesis?. Glia. 2012;60:83-95 pubmed publisher
    ..A secondary event, here mimicked by brain-wide disruption of adenosine signaling, is likely required to turn pre-existing subclinical seizures into a clinical seizure phenotype...
  28. Kuo J, Lo C, Chang C, Lin K, Lin M, Chio C. Agmatine-promoted angiogenesis, neurogenesis, and inhibition of gliosis-reduced traumatic brain injury in rats. J Trauma. 2011;71:E87-93 pubmed publisher
    The mechanisms of agmatine-induced neuroprotective effects in traumatic brain injury (TBI) remain unclear. This study was to test whether inhibition of gliosis, angiogenesis, and neurogenesis attenuating TBI could be agmatine stimulated.
  29. Robel S, Berninger B, Gotz M. The stem cell potential of glia: lessons from reactive gliosis. Nat Rev Neurosci. 2011;12:88-104 pubmed publisher
    ..following brain injury, glia outside these niches acquire or reactivate stem cell potential as part of reactive gliosis. Recent studies have begun to uncover the molecular pathways involved in this process...
  30. Chiu M, Elder D, Zuccollo J. Gliosis in neonatal SUDI cases. Acta Paediatr. 2012;101:30-3 pubmed publisher
    ..To review sudden unexpected infant deaths (SUDI) in the first 28 days of life referred to a Coronial Perinatal Forensic Pathology Service over a 10-year period from 2000 to 2009...
  31. Talley Watts L, Sprague S, Zheng W, Garling R, Jimenez D, Digicaylioglu M, et al. Purinergic 2Y1 receptor stimulation decreases cerebral edema and reactive gliosis in a traumatic brain injury model. J Neurotrauma. 2013;30:55-66 pubmed publisher
    ..measurements in both cortical and hippocampal slices also revealed significant neuronal swelling and reactive gliosis. Treatment of mice with 2MeSADP (100??M) or MRS2365 (100??M) 30?min after trauma significantly reduced all post-..
  32. Ganesh B, Chintala S. Inhibition of reactive gliosis attenuates excitotoxicity-mediated death of retinal ganglion cells. PLoS ONE. 2011;6:e18305 pubmed publisher
    Reactive gliosis is a hallmark of many retinal neurodegenerative conditions, including glaucoma...
  33. Yang Q, Wang E, Huang X, Qu W, Zhang L, Xu J, et al. Blocking epidermal growth factor receptor attenuates reactive astrogliosis through inhibiting cell cycle progression and protects against ischemic brain injury in rats. J Neurochem. 2011;119:644-53 pubmed publisher
    ..Our findings indicated that blocking EGFR pathway might attenuate reactive astrogliosis through inhibiting cell cycle progression and protect against ischemic brain injury in rats...
  34. Hagemann T, Jobe E, Messing A. Genetic ablation of Nrf2/antioxidant response pathway in Alexander disease mice reduces hippocampal gliosis but does not impact survival. PLoS ONE. 2012;7:e37304 pubmed publisher
  35. Xu H, Zhang S, Tan G, Zhu H, Huang C, Zhang F, et al. Reactive gliosis and neuroinflammation in rats with communicating hydrocephalus. Neuroscience. 2012;218:317-25 pubmed publisher
    Reactive gliosis has been implicated in injury and recovery patterns associated with hydrocephalus...
  36. de Melo J, Miki K, Rattner A, Smallwood P, Zibetti C, Hirokawa K, et al. Injury-independent induction of reactive gliosis in retina by loss of function of the LIM homeodomain transcription factor Lhx2. Proc Natl Acad Sci U S A. 2012;109:4657-62 pubmed publisher
    ..the LIM homeodomain transcription factor Lhx2 from mature Müller glia leads to the induction of reactive retinal gliosis in the absence of injury...
  37. Vazquez Chona F, Swan A, Ferrell W, Jiang L, Baehr W, Chien W, et al. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function. BMC Neurosci. 2011;12:98 pubmed publisher
    ..To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (..
  38. Durairajan S, Liu L, Lu J, Chen L, Yuan Q, Chung S, et al. Berberine ameliorates ?-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model. Neurobiol Aging. 2012;33:2903-19 pubmed publisher
    ..Our results suggest that BBR provides neuroprotective effects in TgCRND8 mice through regulating APP processing and that further investigation of the BBR for therapeutic use in treating AD is warranted...
  39. Rivera Zengotita M, Yachnis A. Gliosis versus glioma?: don't grade until you know. Adv Anat Pathol. 2012;19:239-49 pubmed publisher
    ..This paper will review some basic principles of gliosis as an astrocytic reaction to a wide range of central nervous system insults and focus on some common diagnostic ..
  40. Baumgart E, Barbosa J, Bally Cuif L, Gotz M, Ninkovic J. Stab wound injury of the zebrafish telencephalon: a model for comparative analysis of reactive gliosis. Glia. 2012;60:343-57 pubmed publisher
    ..Invasive injury in the adult zebrafish telencephalon may therefore provide a useful model to untangle the molecular mechanisms involved in these beneficial glial reactions...
  41. Groeger G, Doonan F, Cotter T, Donovan M. Reactive oxygen species regulate prosurvival ERK1/2 signaling and bFGF expression in gliosis within the retina. Invest Ophthalmol Vis Sci. 2012;53:6645-54 pubmed
    b>Gliosis is the response of glial cells within retinal tissue to injury. It can be beneficial in the short term, but if the response is extended it can lead to scar formation, which contributes to blindness...
  42. Lee M, Chen C, Huang W, Huang M, Chang W, Kuo H, et al. Regulation of chondroitin sulphate proteoglycan and reactive gliosis after spinal cord transection: effects of peripheral nerve graft and fibroblast growth factor 1. Neuropathol Appl Neurobiol. 2011;37:585-99 pubmed publisher
    ..This project studied the effect of PN graft and FGF-1 on white matter degeneration following spinal cord injury...
  43. Coorey N, Shen W, Chung S, Zhu L, Gillies M. The role of glia in retinal vascular disease. Clin Exp Optom. 2012;95:266-81 pubmed publisher
  44. Xu H, Tan G, Zhang S, Zhu H, Liu F, Huang C, et al. Minocycline reduces reactive gliosis in the rat model of hydrocephalus. BMC Neurosci. 2012;13:148 pubmed publisher
    Reactive gliosis had been implicated in injury and recovery patterns associated with hydrocephalus...
  45. Guyton M, Das A, Samantaray S, Wallace G, Butler J, Ray S, et al. Calpeptin attenuated inflammation, cell death, and axonal damage in animal model of multiple sclerosis. J Neurosci Res. 2010;88:2398-408 pubmed publisher
    ..Calpain activity, gliosis, loss of myelin, and axonal damage were attenuated by calpeptin therapy, leading to improved clinical scores...
  46. Aviles Reyes R, Angelo M, Villarreal A, Rios H, Lazarowski A, Ramos A. Intermittent hypoxia during sleep induces reactive gliosis and limited neuronal death in rats: implications for sleep apnea. J Neurochem. 2010;112:854-69 pubmed publisher
    ..Reactive gliosis has a drastic effect on neuronal survival and circuitry and in this study we examined the neuro-glial response in ..
  47. Ke R, Xiong J, Liu Y, Ye Z. Adenosine A2a receptor induced gliosis via Akt/NF-kappaB pathway in vitro. Neurosci Res. 2009;65:280-5 pubmed publisher
    b>Gliosis is characterized by increased expression of glial fibrillary acidic protein (GFAP) and astroglial proliferation, although the mechanism underlying the process is still largely undefined...
  48. East E, Golding J, Phillips J. A versatile 3D culture model facilitates monitoring of astrocytes undergoing reactive gliosis. J Tissue Eng Regen Med. 2009;3:634-46 pubmed publisher
    ..The transition of astrocytes into this reactive phenotype (reactive gliosis) is a potential therapeutic target, but glial scar formation has proved difficult to study in monolayer cultures ..
  49. Kozoriz M, Bechberger J, Bechberger G, Suen M, Moreno A, Maass K, et al. The connexin43 C-terminal region mediates neuroprotection during stroke. J Neuropathol Exp Neurol. 2010;69:196-206 pubmed publisher
    ..These results suggest that astrocytic Cx43 contributed to the regulation of cell death after stroke and support the view that the Cx43 C-terminal region is important in protection in cerebral ischemia...
  50. Hirrlinger P, Ulbricht E, Iandiev I, Reichenbach A, Pannicke T. Alterations in protein expression and membrane properties during Müller cell gliosis in a murine model of transient retinal ischemia. Neurosci Lett. 2010;472:73-8 pubmed publisher
    ..We found the typical indicators of reactive gliosis such as upregulation of glial fibrillary acidic protein...
  51. Zhang D, Hu X, Qian L, O Callaghan J, Hong J. Astrogliosis in CNS pathologies: is there a role for microglia?. Mol Neurobiol. 2010;41:232-41 pubmed publisher
    ..Development of targeted anti-microglial activation therapies might slow or halt the progression of astrogliosis and, therefore, help achieve a more beneficial environment in various CNS pathologies. ..
  52. Burel Vandenbos F, Benchetrit M, Miquel C, Fontaine D, Auvergne R, Lebrun Frenay C, et al. EGFR immunolabeling pattern may discriminate low-grade gliomas from gliosis. J Neurooncol. 2011;102:171-8 pubmed publisher
    ..As overexpression of EGFR has also been described in gliosis, it can be difficult to evaluate EGFR immunolabeling in diffuse low-grade gliomas because of this cell mix...
  53. Schnieder T, Dwork A. Searching for neuropathology: gliosis in schizophrenia. Biol Psychiatry. 2011;69:134-9 pubmed publisher
    ..A sufficiently large autopsy study, weighted toward younger subjects, could provide a definitive answer, which if positive could be a major step toward finding an underlying pathological process...