Allopregnanolone, a Progesterone Metabolite, Is More Effective Than Progesterone in Reducing Cortical Infarct Volume After Transient Middle Cerebral Artery Occlusion

Sayeed, Iqbal; Guo, Qingmin; Hoffman, Stuart W.; Stein, Donald G.

doi:10.1016/j.annemergmed.2005.12.011

Cited by 156 publications

(140 citation statements)

References 64 publications

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“…Another hormone which may be of interest in the treatment of NP-SLE is progesterone. Considering that progesterone and its precursors/ metabolites have been shown to reconstitute the BBB and enhance functional and structural recovery in rodents and patients with brain edema (Shear et al, 2002;Guo et al, 2006;Sayeed et al, 2006), this hormone may prove to be an effective treatment for the edema seen in NP-SLE patients and MRL-lpr mice (van Dam, 1991;Alexander et al, 2003).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Ballok

2007

Brain Research Reviews

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Animal models are extremely useful tools in defining pathogenesis and treatment of human disease. For many years researchers believed that structural damage to the brain of neuropsychiatric (NP) patients lead to abnormal mental function, but this possibility was not extensively explored until recently. Imaging studies of NP-systemic lupus erythematosus (SLE) support the notion that brain cell death accounts for the emergence of neurologic and psychiatric symptoms, and evidence suggests that it is an autoimmunity-induced brain disorder characterized by profound metabolic alterations and progressive neuronal loss. While there are a number of murine models of SLE, this article reviews recent literature on the immunological connections to neurodegeneration and behavioral dysfunction in the Fas-deficient MRL model of NP-SLE. Probable links between spontaneous peripheral immune activation, the subsequent central autoimmune/inflammatory responses in MRL/MpJ-Tnfrsf6 lpr (MRL-lpr) mice and the sequential mode of events leading to Fas-independent neurodegenerative autoimmune-induced encephalitis will be reviewed. The role of hormones, alternative mechanisms of cell death, the impact of central dopaminergic degeneration on behavior, and germinal layer lesions on developmental/regenerative capacity of MRL-lpr brains will also be explored. This model can provide direction for future therapeutic interventions in patients with this complex neuroimmunological syndrome.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Ballok

2007

Brain Research Reviews

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“…For example, in in vitro studies, E 2 and P 4 reduce some effects of glutamate or Aβ exposure on measures of insult to hippocampal neurons (Goodman et al 1996;Nilsen and Brinton 2002). Similarly, administration of E 2 , P 4 , or 3α,5α-THP can have beneficial effects in whole animal models of aging and neuronal compromise (i.e., seizure, cortical contusion, ischemia, and diabetic neuropathy models; Asbury et al 1998;Cervantes et al 2002;Charalampopoulos et al 2006;Ciriza et al 2004;Frye and Rhodes 2005;Frye and Walf 2008;Leonelli et al 2007;Nilsen and Brinton 2002;Rhodes and Frye 2004;Roof et al 1994;Sayeed et al 2006). Progestogens can also decrease anxiety-like, fear, and depressive-like behavior among young and aged female rats or mice (Frye et al , 2006bFrye and Rhodes 2006;Martinez-Mota et al 1999;Rodriguez-Landa et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Frye

Walf

2009

AGE

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Although anxiety and depression are not the core symptoms of Alzheimer's Disease (AD), there are changes observed in mood in those with AD, as well as in the aging population. Anxiety and depression may be influenced by progesterone P 4 and/or its neuroactive metabolites, dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (3α,5α-THP). To begin to investigate progestogens' role in AD, a double transgenic mouse model of early-onset familial AD that cooverexpresses mutant forms of amyloid precursor protein (APPswe) and presenilin 1 Δ exon 9 mutation was utilized. As such, the effects of long-term (from 6 to 12 months of age) administration of P 4 to ovariectomized (ovx) wildtype and APPswe+PSEN1Δe9 mice for changes in affective behavior was investigated. APPswe+PSEN1Δ9 mutant mice had increased anxiety-like (i.e., increased emergence latencies, decreased time spent on the open quadrants of the elevated zero maze) and increased depressive-like behavior (i.e., increased time spent immobile) than did wildtype mice. Compared to vehicle-administration, P 4 administration (which produced physiological circulating P 4 , DHP, and 3α,5α-THP levels, particularly in the wildtype mice) decreased depressant-like behavior in the forced swim test. These effects occurred independent of changes in general motor behavior/coordination, pain threshold, and plasma corticosterone levels. Thus, the APPswe+PSEN1Δ9 mutation alters affective behavior, and P 4 treatment reversed depressive-like behavior.

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“…Past reports find that administration of P 4 with E 2 to OVX rats, increases hippocampal spine density (Woolley et al 1996, Miranda et al 1999 and some of these effects are likely due to actions through its metabolism to 3a,5a-THP. In support, 3a,5a-THP has trophic effects to enhance central and peripheral myelination, it is neuroprotective in traumatic brain injury and ischemic stroke, and improves functional outcome after trauma (Magnaghi et al 2001, Schumacher et al 2001, Ghoumari et al 2003, Sayeed et al 2006, VanLandingham et al 2007). As such, trophic effects of 3a,5a-THP may underlie some of the neuroprotective aspects that have been reported with motherhood in aging (Gatewood et al 2005, Pawluski & Galea 2007.…”

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confidence: 99%

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

Paris¹,

Frye²

2008

Reproduction

116

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Ovarian hormone elevations are associated with enhanced learning/memory. During behavioral estrus or pregnancy, progestins, such as progesterone (P 4 ) and its metabolite 5a-pregnan-3a-ol-20-one (3a,5a-THP), are elevated due, in part, to corpora luteal and placental secretion. During 'pseudopregnancy', the induction of corpora luteal functioning results in a hormonal milieu analogous to pregnancy, which ceases after about 12 days, due to the lack of placental formation. Multiparity is also associated with enhanced learning/memory, perhaps due to prior steroid exposure during pregnancy. Given evidence that progestins and/or parity may influence cognition, we investigated how natural alterations in the progestin milieu influence cognitive performance. In Experiment 1, virgin rats (nulliparous) or rats with two prior pregnancies (multiparous) were assessed on the object placement and recognition tasks, when in high-estrogen/P 4 (behavioral estrus) or low-estrogen/P 4 (diestrus) phases of the estrous cycle. In Experiment 2, primiparous or multiparous rats were tested in the object placement and recognition tasks when not pregnant, pseudopregnant, or pregnant (between gestational days (GDs) 6 and 12). In Experiment 3, pregnant primiparous or multiparous rats were assessed daily in the object placement or recognition tasks. Females in natural states associated with higher endogenous progestins (behavioral estrus, pregnancy, multiparity) outperformed rats in low progestin states (diestrus, non-pregnancy, nulliparity) on the object placement and recognition tasks. In earlier pregnancy, multiparous, compared with primiparous, rats had a lower corticosterone, but higher estrogen levels, concomitant with better object placement performance. From GD 13 until post partum, primiparous rats had higher 3a,5a-THP levels and improved object placement performance compared with multiparous rats.

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Allopregnanolone, a Progesterone Metabolite, Is More Effective Than Progesterone in Reducing Cortical Infarct Volume After Transient Middle Cerebral Artery Occlusion

Cited by 156 publications

References 64 publications

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Progesterone reduces depression-like behavior in a murine model of Alzheimer’s Disease

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

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