Inter-ictal and post-ictal circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in epileptic children

被引:16
作者
Grosso, S [1 ]
Luisi, S [1 ]
Mostardini, R [1 ]
Farnetani, M [1 ]
Cobellis, L [1 ]
Morgese, G [1 ]
Balestri, P [1 ]
Petraglia, F [1 ]
机构
[1] Univ Siena, Dept Pediat Obstetr & Reprod Med, I-53100 Siena, Italy
关键词
allopregnanolone; neurosteroids; neuroactive steroids; epilepsy;
D O I
10.1016/S0920-1211(03)00042-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Alloprenanolone belongs to a group of neuroactive steroid hormones, or neurosteroids, synthesized and acting within the brain and is as a potent endogenous positive modulator of GABA(A) receptor complex. Administration of allopregnanolone protects rats against pentylentetrazol, bicuculline, kainic acid, and picrotoxin-induced seizures. We investigated serum allopregnanolone levels in children with active epilepsy at pubertal Tanner's stage I (n = 52). Blood specimens were collected at least 12 h after a seizure (inter-ictal). In a subgroup of patients (n = I I), specimens were also collected within 30 min from a seizure attack (post-ictal). Healthy age-matched children (n = 18) served as controls. Serum allopregnanolone was measured by radioimmunoassay using a polyclonal antiserum. The inter-ictal serum allopregnanolone levels in the epileptic children were not statistically different from those detected in the control group. whereas post-ictal levels were significantly higher than the inter-ictal ones (P = 0.000 1). In this subgroup of patients allopregnanolone levels decreased to the basal values during the following 12 h. Serum allopregnanolone levels may therefore reflect changes in neuronal excitability, and allopregnanolone appears to be a reliable circulating marker of epileptic seizures. It is possible that increased post-ictal serum levels of allopregnanolone may play a role in modulating neuronal excitability and may represent an endogenous mechanism of seizure control. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:29 / 34
页数:6
相关论文
共 31 条
[11]   NEUROACTIVE STEROID SENSITIVITY IN WITHDRAWAL SEIZURE-PRONE AND SEIZURE-RESISTANT MICE [J].
FINN, DA ;
ROBERTS, AJ ;
CRABBE, JC .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1995, 19 (02) :410-415
[12]   Anti-seizure effects of progesterone and 3α,5α-THP in kainic acid and perforant pathway models of epilepsy [J].
Frye, CA ;
Scalise, TJ .
PSYCHONEUROENDOCRINOLOGY, 2000, 25 (04) :407-420
[13]   Infusion of 3α,5α-THP to the pontine reticular formation attenuates PTZ-induced seizures [J].
Frye, CA ;
Manjarrez, J ;
Camacho-Arroyo, I .
BRAIN RESEARCH, 2000, 881 (01) :98-102
[14]   3α,5α-THP in the raphe magnus attenuates PTZ-induced myoclonic seizures [J].
Frye, CA ;
Muscatiello, NA .
BRAIN RESEARCH, 2001, 911 (02) :146-151
[15]   THE NEUROSTEROID 3-ALPHA,5-ALPHA-THP HAS ANTISEIZURE AND POSSIBLE NEUROPROTECTIVE EFFECTS IN AN ANIMAL-MODEL OF EPILEPSY [J].
FRYE, CA .
BRAIN RESEARCH, 1995, 696 (1-2) :113-120
[16]   Circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in women with partial epilepsy in the postcritical phase [J].
Galli, R ;
Luisi, M ;
Pizzanelli, C ;
Monteleone, P ;
Casarosa, E ;
Iudice, A ;
Murri, L .
EPILEPSIA, 2001, 42 (02) :216-219
[17]   Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders [J].
Gasior, M ;
Carter, RB ;
Witkin, JM .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1999, 20 (03) :107-112
[18]   Circulating levels of allopregnanolone in humans: Gender, age, and endocrine influences [J].
Genazzani, AR ;
Petraglia, F ;
Bernardi, F ;
Casarosa, E ;
Salvestroni, C ;
Tonetti, A ;
Nappi, RE ;
Luisi, S ;
Palumbo, M ;
Purdy, RH ;
Luisi, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (06) :2099-2103
[19]  
JUNGTESTAS I, 1989, ENDOCRINOLOGY, V125, P2083
[20]   Ganaxolone for treating intractable infantile spasms: a multicenter, open-label, add-on trial [J].
Kerrigan, JF ;
Shields, WD ;
Nelson, TY ;
Bluestone, DL ;
Dodson, WE ;
Bourgeois, BFD ;
Pellock, JM ;
Morton, LD ;
Monaghan, EP .
EPILEPSY RESEARCH, 2000, 42 (2-3) :133-139