Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration

McCann, Mondona; O’Callaghan, James P.; Martin, Parthena M.; Bertram, Timothy A.; Streit, Wolfgang J.

doi:10.1016/0306-4522(95)00526-9

Cited by 106 publications

(55 citation statements)

References 35 publications

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“…28,82,83 Our IHC results support this time course, indicating injury-induced astrogliosis in the insula and amygdala at 6 months postinjury, but less activation of microglia (only significant in the amygdala), suggesting that microglial activation may precede astrocytic activation and modulate the onset and maintenance of astrogliosis. 27,[84][85][86][87][88] Lower levels of microglia expression could be the result of assessment at 6 months postinjury, when microglia may have returned to a quiescent or surveying state, 28,89 whereas astrocytic activation persists in a long-lasting, self-perpetuating…”

Section: Discussionmentioning

confidence: 99%

Reversal of Established Traumatic Brain Injury-Induced, Anxiety-Like Behavior in Rats after Delayed, Post-Injury Neuroimmune Suppression

Rodgers

Deming

Bercum

et al. 2014

Journal of Neurotrauma

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Traumatic brain injury (TBI) increases the risk of neuropsychiatric disorders, particularly anxiety disorders. Yet, there are presently no therapeutic interventions to prevent the development of post-traumatic anxiety or effective treatments once it has developed. This is because, in large part, of a lack of understanding of the underlying pathophysiology. Recent research suggests that chronic neuroinflammatory responses to injury may play a role in the development of post-traumatic anxiety in rodent models. Acute peri-injury administration of immunosuppressive compounds, such as Ibudilast (MN166), have been shown to prevent reactive gliosis associated with immune responses to injury and also prevent lateral fluid percussion injury (LFPI)-induced anxiety-like behavior in rats. There is evidence in both human and rodent studies that post-traumatic anxiety, once developed, is a chronic, persistent, and drug-refractory condition. In the present study, we sought to determine whether neuroinflammation is associated with the long-term maintenance of post-traumatic anxiety. We examined the efficacy of an anti-inflammatory treatment in decreasing anxiety-like behavior and reactive gliosis when introduced at 1 month after injury. Delayed treatment substantially reduced established LFPI-induced freezing behavior and reactive gliosis in brain regions associated with anxiety and continued neuroprotective effects were evidenced 6 months post-treatment. These results support the conclusion that neuroinflammation may be involved in the development and maintenance of anxiety-like behaviors after TBI.

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Section: Discussionmentioning

confidence: 99%

Reversal of Established Traumatic Brain Injury-Induced, Anxiety-Like Behavior in Rats after Delayed, Post-Injury Neuroimmune Suppression

Rodgers

Deming

Bercum

et al. 2014

Journal of Neurotrauma

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“…In this regard, it is noteworthy that numerous CNS insults (e.g. kainic acid, trimethyltin, traumatic brain injury) that have been shown to increase C-tau formation (Irazuzta et al, 2001, Gabbita et al, 2005 also increase GFAP, a marker of reactive gliosis (Brock and O'Callaghan, 1987, McCann et al, 1996, Koczyk and Oderfeld-Nowak, 2000, Little et al, 2002, Wang et al, 2004a, Guo et al, 2006. Furthermore, the results of the present experiment, in which the number of C-tau immunoreactive cells has been shown to be increased in the striatum following METH or AMPH treatment, but not MDMA or PMA treatment, are in agreement with previous studies that have examined GFAP immunoreactivity or protein expression.…”

Section: Discussionmentioning

confidence: 99%

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

et al. 2007

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The present study quantified the cleaved form of the microtubule associated protein tau (cleaved MAP-tau, C-tau), a previously demonstrated marker of CNS toxicity, following the administration of monoamine-depleting regimens of the psychostimulant drugs amphetamine (AMPH), methamphetamine (METH), ±3,4-methylenedioxymethamphetamine (MDMA), or paramethoxyamphetamine (PMA) in an attempt to further characterize psychostimulant-induced toxicity. A dopamine (DA)-depleting regimen of AMPH produced an increase in C-tau immunoreactivity in the striatum, while a DA-and serotonin (5-HT)-depleting regimen of METH produced an increase in the number of C-tau immunoreactive cells in the striatum and CA2/CA3 and dentate gyrus regions of the hippocampus. MDMA and PMA, two psychostimulant drugs that produce selective 5-HT depletion in the striatum, had no effect on C-tau immunoreactivity in the striatum or hippocampus. Furthermore, 5,7-dihydroxytryptamine (5,7-DHT), an established 5-HT selective neurotoxin, did not produce an increase in C-tau immunoreactivity. Dual fluorescent immunocytochemistry with antibodies to GFAP and C-tau indicated that C-tau immunoreactivity was present in astrocytes, not neurons, suggesting that increased C-tau may be an alternative indicator of reactive gliosis. The present results are consistent with previous findings that the DA-depleting psychostimulants AMPH and METH produce reactive gliosis whereas the 5-HT-depleting drugs MDMA and PMA, as well as the known 5-HT selective neurotoxin 5,7-DHT, do not produce an appreciable glial response. Keywords methamphetamine; 3,4-methylenedioxymethamphetamine; amphetamine; paramethoxyamphetamine; 5,7-dihydroxytryptamine; toxicity Methamphetamine (METH) and ±3,4-methylenedioxymethamphetamine (MDMA) are substituted phenylethylamines whose popularity among young adults continues to be a public

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“…A recent metaanalysis (1989-2009, including 91 treatments and over 200 pre-clinical studies) assessed the impact of pharmacological agents on cognitive, motor and behavioral outcomes in rats following TBI, and the results revealed that almost no treatment improves behavioral outcomes, including anxiety, depression and aggression (90). Three studies that have been found to be effective in reducing anxietylike aftermaths following TBI, as evidenced by increased exploratory behavior in open field and elevated plus tests in treated animals, utilized magnesium, resveratrol and progesterone (66,79,85). Although the mechanism of action for magnesium treatment is unknown, the neuroprotective effect is likely due to reductions in glutamate excitotoxicity, mitochondrial damage, and apoptosis (91).…”

Section: Preliminary Study 1: Evidence For Prevention Of Post-traumatmentioning

confidence: 99%

Section: Inflammation and Post-traumatic Anxietymentioning

confidence: 99%

Targeting Microglia to Prevent Post-Traumatic Epilepsy

Barth¹

2014

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE July 2014 REPORT TYPE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)The Regents of the University of Colorado Boulder, CO 80303-1058 31 AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe purpose of this research project is to explore anti-epileptogenic strategies in and animal model of post-traumatic epilepsy (PTE) using lateral fluid percussion injury (LFPI). Our focus is on attenuating damaging effects of hyperexcitability in the brain induced by inflammation resulting from glial cell immune responses to trauma. We are exploring two drugs, MN166 and SLC022, that are known to suppress post-traumatic glial activation and thus inflammation to evaluate their effectiveness in preventing epileptogenesis in the LFPI model of PTE. In the first project year we developed a high-speed video/EEG recording and analysis system for rapid quantification of chronically recorded epileptiform activity in multiple (24-32) subjects. With this system we became expert in identifying epileptiform versus normal video/EEG activity in the rodent and discovered an important source of artifact currently being interpreted in other published reports as seizure activity. We developed a pilocarpine model of temporal lobe epilepsy to explore the effectiveness of glial cell (neuroimmune) attenuation in preventing or limiting epileptogenesis (development of epilepsy) in this rapidly developing model. We explored numerous changes in the LFPI model to produce earlier developing signs of epilepsy, increasing the probability of succeeding in our long-term study of epileptogenesis following traumatic brain injury. Perhaps the most important outcome of this work was the negative finding that much published work concerning PTE with the LFPI model has not properly examined controls. Both injured and uninjured rats displ...

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Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration

Cited by 106 publications

References 35 publications

Reversal of Established Traumatic Brain Injury-Induced, Anxiety-Like Behavior in Rats after Delayed, Post-Injury Neuroimmune Suppression

Reversal of Established Traumatic Brain Injury-Induced, Anxiety-Like Behavior in Rats after Delayed, Post-Injury Neuroimmune Suppression

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

Targeting Microglia to Prevent Post-Traumatic Epilepsy

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