Elevated cyclic GMP concentrations in rat adrenal cortex after dexamethasone administration.

The levels of cGMP and cAMP were measured in the fasciculata-reticularis zona of the adrenal cortex in both intact and hypophysectomized young adult male rats. After administration of a single dose of dexamethasone to intact rats, cGMP levels were elevated 2–4 fold after 4hr and returned to control level after 8hr. At the same time, cAMP concentrations were moderately lowered. In hypophysectomized rats dexamethasone administration was followed by a similar increase in the cGMP level, the basal cAMP concentrations were not altered by dexamethasone. Our data suggest that dexamethasone might have a direct effect on cGMP concentration in the adrenal cortex of the rat.     

Dual effects of dopamine in rat adrenal glomerulosa cells

The effects of dopamine (DA) on cAMP production and aldosterone secretion were compared in freshly isolated cells and in primary cultures of rat adrenal glomerulosa cells. Under isolated conditions, glomerulosa cells exhibited dopamine receptors from DA-1 and DA-2 subclass, whereas in cultured conditions, where cells are very sensitive to their known stimuli, cells only exhibited dopamine receptors from the DA-1 subclass. Moreover, unlike freshly isolated cells, dopamine stimulated both cAMP production and aldosterone secretion in 3-day cultured preparations. These effects were receptor specific since they were completely suppressed by Scherring 23390 (a specific DA-1 antagonist) and were unaffected by a beta-adrenergic antagonist. As in vivo rat adrenal cortex contains DA, we discuss a possible involvement of this neurotransmitter in the regulation of aldosterone secretion.     

Regulation of rat and bovine adrenal metabolism of polycyclic aromatic hydrocarbons by adrenocorticotropin and 2,3,7,8-tetrachlorodibenzo-p-dioxin

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on polycyclic aromatic hydrocarbon (PAH) metabolism and steroidogenesis in primary cultures of bovine adrenal cortical (BAC) and rat adrenal cortical (RAC) cells have been examined. Remarkably TCDD is an ineffective inducer (15-50%) of PAH metabolism in confluent BAC cells and completely antagonizes a 5-fold induction by benz[alpha]anthracene (BA). In the same concentration range (EC50 5 X 10(-11) M) TCDD suppresses steroidogenesis through an effect on cholesterol metabolism. Adrenocorticotropin (ACTH) and cAMP also suppress PAH metabolism at concentrations which stimulate steroidogenesis (10(-7) M). In RAC cells ACTH potently induces PAH metabolism (7-fold) at a comparable concentration to the stimulation of steroidogenesis. Parallel stimulation of PAH metabolism and steroidogenesis by cAMP suggest that ACTH induction of PAH metabolism is mediated by cAMP. TCDD induces PAH metabolism (2.8-fold, EC50 8 X 10(-11) M) at similar concentrations to the inhibitory effect in BAC cells and this action is additive with ACTH induction. In male rats in vivo TCDD induces adrenal microsomal PAH metabolism (72%) and is more effective in this respect than 3-methylcholanthrene (3MC). Rabbit antibodies against rat liver cytochrome P-450c (the major TCDD-inducible liver form) inhibited the TCDD-induced adrenal metabolism of 7,12-dimethylbenz[alpha]anthracene (DMBA), which also exhibited regioselectivity typical of metabolism by P-450c. Constitutive adrenal microsomal metabolism, which exhibited regioselectivity of DMBA metabolism comparable to the ACTH-sensitive cellular metabolism, was not affected by anti-P-450c. It is concluded that ACTH and TCDD induce distinct forms of cytochrome P-450 in RAC cells and that the latter represents a typical Ah-receptor mediated response. The anomalous effect on PAH metabolism in BAC cells that parallels inhibition of steroidogenesis may derive from repression of a distinct adrenal form of P-450 by the TCDD-Ah-receptor complex.     

Effects of dietary cholesterol on pyroglutamyl aminopeptidase activity in mouse frontal cortex, pituitary, and adrenal glands.

Pyroglutamyl aminopeptidase (pGluAP) is an omega peptidase that hydrolyzes biologically active peptides, such as thyrotropin-releasing hormone (TRH), with neuronal and extraendocrine functions. We analyzed the effects of a cholesterol-enriched diet on soluble and membrane-bound pGluAP activity in frontal cortex, pituitary and adrenal glands of male and female mice using fluorimetric assays. Significant increases were observed in soluble pGluAP activity in the frontal cortex and adrenal glands in males and in the pituitary in females. Membrane-bound pGluAP activity was increased in the frontal cortex and pituitary of males and females after the mice were fed a cholesterol-enriched diet. These increases may produce changes in the metabolism of endogenous substrates, including TRH, which may be related to alterations in its neuromodulator functions and to the possible relationship between TRH and other neurotransmitter systems.     

Evidence suggesting a role for cyclic nucleotides in acrosome reactions of hamster sperm in vitro

There have been conflicting reports concerning the involvement of cyclic nucleotides in sperm capacitation. We have examined the effects of micromolar concentrations of dibutyryl cyclic AMP (Bt2cAMP) and of the phosphodiesterase inhibitors SQ20009 and ICI63,197 on hamster sperm incubated under in vitro capacitating conditions. Washed hamster sperm were incubated in a capacitation media containing bovine serum albumin, and a protein-free "motility-factor" from bovine adrenal cortex. Incubation for 3.5 hours was followed by addition of one of the compounds (0.1-10 microM) or control buffer. At the time of addition and after 30-120 minutes further incubation, sperm were examined by phase contrast microscopy. The final motility was similar to the initial motility (50-70%) and the same in incubation of controls or experimental compounds. Bt2cAMP, SQ20009, and ICI63,197 at these concentrations stimulated acrosome reactions to a statistically significant extent (P less than 0.005) compared to controls. Activation was stimulated to a varying degree by all three experimental compounds. These results suggest a role for cyclic nucleotides in capacitation and the acrosome reaction of hamster sperm.     

儿茶酚胺类激素在海洛因成瘾中的作用

目的：探索儿茶酚胺类激素在海洛因成瘾中的作用。方法：肌肉注射利血平后再给予海洛因,用放射免疫法检测血液和脑组织中多巴胺（dopamine,DA）、环磷酸腺苷（cMAP）、环磷酸鸟苷（cMGP）水平。结果：利血平组大鼠未出现明显的戒断反应症状。放射免疫法检测发现,血液、中脑腹侧背盖区（ventral tegmental area,VTA）、大脑前额叶皮（prefrontal cortex,PFC）、海马（hippocampus,Hipp）中cAMP水平：利血平纽比对照组和海洛因组分别升高35．36％和15．53％、24．08％和8．53％、15．66％和8．13％、21．95％和8．40％;PFC、Hipp、纹状体（striatum）、伏隔核（nueleus aceumbens,NAc）中DA水平：利血平组比对照组和海洛因组分别降低74．09％和82．86％、81．06％和82．23％、91．62％和86．55％、84．35％和90．63％;脑组织cGMP的含量均低于对照组。神经电生理检测发现,海洛因和利血平组,大鼠的脑电图、心电图和肌梭放电图与对照组比,均发生明显的改变。结论：儿茶酚胺类激素是引起海洛因成瘾的关键因素。     

Effects of orexin on cultured porcine adrenal medullary and cortex cells

New orexigenic peptides called orexins have recently been described in the neurons of the lateral hypothalamus and perifornical area. No orexins have been found in the adipose tissues or visceral organs, including the adrenal gland. However, expression of the orexin receptor (OXR) in the rat adrenal gland has been reported. With regard to the effects of orexins on peripheral organs, we previously reported that orexins suppress catecholamine synthesis and secretion in the rat pheochromocytoma cell line PC12. To further clarify the pharmacological effects of orexins on peripheral organs, we examined the effects of orexin-A on catecholamine, cortisol, and aldosterone secretion, using cultured porcine adrenal glands. We initially confirmed the expression of the orexin receptor (OXR-1) in cultured porcine adrenal medulla and cortex. Orexin-A (1000 nM) significantly increased the release of both epinephrine (E) and norepinephrine (NE) from porcine adrenal medullary cells. Similarly, orexin-A (> or = 100 nM) significantly increased the release of both cortisol and aldosterone from porcine adrenal cortex cells. Orexin-A (100 nM) significantly inhibited basal and the PACAP-induced increase in cAMP levels in adrenal medullary cells. Conversely, orexin-A (>o = 100 nM) significantly increased the cAMP level in adrenal cortex cells. These results indicate that orexin-A induces the release of catecholamine from porcine adrenal medullary cells, and aldosterone and cortisol from the cortex cells and has opposite effects on cAMP levels in adrenal medulla and cortex.     

Inhibition of adrenal steroid metabolism by administration of 1-aminobenzotriazole to guinea pigs

Prior in vitro investigations demonstrated that the P450 suicide substrate, 1-aminobenzotriazole (ABT), was a potent inhibitor of xenobiotic metabolism but had no effect on steroidogenic enzymes in the guinea pig adrenal cortex. Studies were done to determine if ABT administration to guinea pigs in vivo also selectively inhibited adrenal xenobiotic metabolism. At single doses of 25 or 50 mg/kg, ABT effected rapid decreases in spectrally detectable adrenal P450 concentrations. The higher dose caused approx. 75% decreases in microsomal and mitochondrial P450 levels within 2 h. The decreases in P450 were sustained for 24 h but concentrations returned to control levels within 72 h. Accompanying the ABT-induced decreases in adrenal P450 content were proportionately similar decreases in P450-mediated xenobiotic and steroid metabolism. Microsomal benzo(a)pyrene hydroxylase, benzphetamine N-demethylase, 17-hydroxylase and 21-hydroxylase activities were decreased to 20–25% of control values by the higher dose of ABT. Mitochondrial 11β-hydroxylase and cholesterol sidechain cleavage activities were similarly diminished by ABT treatment. Adrenal 3β-hydroxysteroid dehydrogenase activity, by contrast, was not affected by ABT, indicating specificity for P450-catalyzed reactions. The results demonstrate that ABT in vivo is a non-selective inhibitor of adrenal steroid- and xenobiotic-metabolizing P450 isozymes. The absence of ABT effects on steroid metabolism in vitro suggests that an extra-adrenal metabolite may mediate the in vivo inhibition of steroidogenesis.     

Adrenal glucocorticoid function and cytoplasmic dehydrogenase activity in the presnece of mechanical and toxic liver damage]

Against the background of low steroid metabolism in the liver there was noted some decrease in the rate of corticosterone synthesis by the adrenal gland sections, and also, a decrease in the dehydrogenase activity in the cytoplasm of adrenal cells in male rats 48 hours after partial hepatectomy, as compared to the sham-operated animals. These changes resulted from suppression of the central mechanisms of stress realization due to the lowered steroid metabolism. Intraperitoneal administration of carbon tetrachloride (0.1 ml per 100 g of body weight) at the same periods led to a significant intensification of the steroidogenesis in the adrenal tissue and to the activation of NAD-dependent dehydrogenases in the cytoplasm. The role of toxic injury of the glands in the changes of the functional state of the adrenal cortex cells is discussed.     

Ovine fetal adrenal maturation at term and during fetal ACTH administration: evidence that the modulating effect of cortisol may involve cAMP

Exogenous ACTH1-24 promotes adrenal maturation in fetal sheep, and this effect appears to be modulated in part by cortisol (Challis et al. 1985). We have examined whether similar changes in adrenal metabolism of progesterone occur with ACTH-induced labour as at spontaneous term and whether the site of cortisol modulation is on adrenal steroidogenesis or at the level of cAMP generation. Chronically catheterized fetal sheep were infused in utero for 100 h between days 127 and 131 of pregnancy with P-ACTH, P-ACTH + metopirone, P-ACTH + metopirone + cortisol, or saline. After 100 h the metabolism of [3H]progesterone was measured in adrenal homogenates. Similar incubations were performed with adrenal tissue from fetal sheep at day 130 of pregnancy and at spontaneous labour. In the treatment groups of sheep, cAMP output by dispersed adrenal cells in response to ACTH added in vitro was also determined. Similar qualitative patterns of [3H]progesterone metabolism were found in adrenal homogenates after in vivo ACTH or at term. At both times there was an increase in cortisol and in total 17 alpha-hydroxycorticosteroid accumulation and also evidence for increased activity of 11 beta-hydroxylase enzyme. The formation of total 17 alpha-hydroxycorticosteroids was not affected significantly by concurrent treatment in vivo with metopirone +/- cortisol. The accumulation of cAMP in vitro was increased after in vivo ACTH, attenuated after ACTH + metopirone, but statistical significance over controls was restored after ACTH + metopirone + cortisol treatment. We conclude that ACTH-induced labour and spontaneous parturition in sheep is associated with qualitatively similar changes in progesterone metabolism by the fetal adrenal gland.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of several structuro-functional parameters of the liver and adrenal cortex in mice of different genetic strains under physiologically normal conditions]

In adult male mice CBA and C57BL there were revealed differences in the morphometric characteristics of the subcellular organization of hepatocytes, as well as in the indices of functional capacity of the adrenal cortex and the rate of metabolism of steroid hormones in the liver. In animals of the strains under study the levels of steroid hormones production by the adrenal cortex and the rate of gross metabolism of steroid hormones in the liver were characterized by inverse relationship. Structural-functional indices of the adrenal cortex and the liver are supposed to cause different liver responses in these strains of mice to the influence of the alterating factors.     

Alternate cadmium exposure differentially affects amino acid metabolism within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats.

This work was designed to analyze the possible changes in glutamate, aspartate and glutamine content induced by cadmium exposure in the hypothalamus, striatum and prefrontal cortex of rats, using an alternate schedule of metal administration. Pubertal-adult differences were also evaluated. In adult control rats, glutamate and aspartate contents in the anterior hypothalamus decreased as compared to pubertal controls. After cadmium administration from day 30 to 60 of life, the content of anterior hypothalamic glutamate and aspartate diminished. In adult control animals, the glutamine content increased in mediobasal hypothalamus as compared to pubertal controls. After cadmium exposure from day 30 to 60 of life, the mediobasal glutamine content increased, and after cadmium treatment from day 60 to 90 of life, the mediobasal aspartate content decreased. In adult control rats the content of glutamine, glutamate and aspartate of the posterior hypothalamus decreased significantly. After cadmium administration in pubertal animals, posterior hypothalamic contents of glutamine, glutamate and aspartate diminished. Cadmium treatment of adult animals caused a decrease in glutamine content, as compared to controls. In adult control rats, only glutamate and aspartate content increased in the prefrontal cortex as compared to the values found in pubertal controls. When cadmium was administered to adult animals, only the aspartate content decreased. In the striatum, cadmium decreased the glutamine and aspartate contents when administered from day 60 to 90 of life. These data suggest that cadmium differentially affects amino acid metabolism in the hypothalamus, striatum and prefrontal cortex. Age-dependent effects of cadmium on these brain areas appeared to have occurred.     

Participation of cyclic nucleotides, protein kinase A and C in realization of n-acylethanolamine action in human adrenocortical cells

The messenger mechanisms mediating N-acylethanolamines (NAE) regulatory signals in the adrenal cortex were studied. An analysis of the mechanisms of realization of NAE effects in the post-operation human adrenal cortex was carried out in vitro. Influence of NAE mix on cAMP and cGMP level, protein kinase A and C activity in sub-cellular fraction of adrenocorticocytes and homogenates of conditionally normal adrenal cortex tissues was investigated. It was shown, that N-acylethanolamines treatment resulted in a decrease of cAMP level in adrenocortical cells. cGMP level is not changed in these conditions. The rise of protein kinase C activity was obtained in the membrane fraction after N-acylethanolamines in vitro treatment (3.3 microg/ml). Activity of cAMP-dependent protein kinase A significantly decreased in cytosol fraction of adrenocorticocytes. It was concluded, that steroid genesis activation is determined by protein kinase C activation, inhibition is determined by cAMP-dependent messenger system.     

Effect of haloperidol on cyclic AMP and inositol trisphosphate in rat striatum in vivo.

To investigate the effect of haloperidol (HAL) on second messengers in the brain striatum, the concentrations of cAMP and inositol trisphosphate (IP-3) were measured in the striatum of rats in vivo after intravenous administration of HAL, and their concentrations were compared with the severity of catalepsy and changes in dopamine (DA) metabolism in the striatum. Catalepsy developed both in the animals treated with 5 mg/kg and those with 0.5 mg/kg of HAL, but it appeared earlier, and the period of severe catalepsy was longer in the former than in the latter. In the animals treated with 5 mg/kg of HAL, DOPAC and HVA began to increase at 20 min after administration, and their percent increases were correlated with the severity of catalepsy. In the 5 mg/kg animals, both cAMP and IP-3 increased. The IP-3 showed a delayed peak but a greater increase as compared with the cAMP. In the 0.5 mg/kg animals, only IP-3 increased. These findings suggest that HAL might affect not only the adenylate cyclase system but also the phosphoinositide response in the striatum. Moreover, the changes in the phosphoinositide response might be secondarily induced by the blocking of D-2 receptors by HAL.     

Effect of pentagastrin on steroid secretion and proliferative activity of regenerating rat adrenal cortex

The effects of three subcutaneous injections of 3 nmol/100 g body weight of the cholecystokinin type 2 (CCK2) receptor agonist pentagastrin on adrenocorticotrophic hormone (ACTH) and corticosterone secretion and proliferative activity of regenerating rat adrenal cortex were investigated. Pentagastrin did not alter either ACTH and corticosterone plasma concentrations or the adrenal mitotic index at day 5 of regeneration. In contrast, it increased (by about 50%) the adrenal mitotic index at day 8 of regeneration, and the effect was blocked by the simultaneous administration of equimolar doses of the CCK2-receptor antagonist PD-135,158. It is suggested that the activation of CCK2 receptors exerts a growth promoting action on the regenerating rat adrenal cortex.     

A cytochemical study of the effect of tuftsin on the enzyme activity in functionally different formations of the brain in rats]

Quantitative cytochemical methods in functionally different rat brain formations (sensomotor cortex, visual cortex, nucleus caudatus, hippocampus) showed the peculiarities of the effect of tuftsin on the activity of some enzymes (the oxidative, neurotransmitter and protein metabolism enzymes) 15 min and 3 days after its single administration. No changes of activity of neurotransmitter metabolism enzymes (monoamine oxidase, acetylcholinesterase) were registered cytochemically. The specificity of the neuro-tropical effect of tuftsin on protein (activity of aminopeptidase and acid phosphatase) and oxidative (activity of glutamate dehydrogenase and glucose-6-phosphate dehydrogenase) metabolism in different functional brain systems is discussed.     

Stress-Related Changes in Cerebral Catecholamine and Indoleamine Metabolism: Lack of Effect of Adrenalectomy and Corticosterone

The concentrations of catecholamine and indoleamine metabolites were measured in intact and adrenalectomized mice to determine whether adrenal hormones mediate or modulate the stress-induced responses. Thirty minutes of footshock resulted in significant increases of the ratios of the dopamine (DA) catabolite, dihydroxyphenylacetic acid (DOPAC), to DA in prefrontal cortex, nucleus accumbens, striatum, hypothalamus, and brainstem, and of homovanillic (HVA)/DA ratios in nucleus accumbens, striatum, amygdala, and hypothalamus. Ratios of 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine (NE) were also increased in prefrontal cortex, nucleus accumbens, septum, amygdala, hypothalamus, hippocampus, and brainstem. The concentration of NE was decreased in amygdala. 5-Hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT, serotonin) ratios and free tryptophan were also increased in every brain region. Very similar data were obtained from mice restrained for 30 min. Adrenalectomy resulted in increased HVA/DA ratios in prefrontal cortex and striatum, and 5-HIAA/5-HT in septum. The stress-related changes were largely similar in adrenalectomized mice. Significant interactions between adrenalectomy and footshock treatment occurred in prefrontal cortical DOPAC/DA and hypothalamic NE which was depleted only in adrenalectomized mice, suggesting tendencies for these measures to be more responsive in adrenalectomized mice. Corticosterone administration (0.5-2.0 mg/kg s.c.) which resulted in plasma concentrations in the physiological range did not alter the concentrations of the cerebral metabolites measured in any region. We conclude that adrenal hormones do not mediate cerebral catecholamine or indoleamine metabolism in stress, although adrenalectomy may affect HVA and 5-HIAA metabolism, and there was a tendency for catecholamines to be more sensitive to stress in adrenalectomized animals.     

A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat

Background

We aimed to further understand the relationship between cAMP concentration and mnesic performance.

Methods and Findings

Rats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p.), rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p.) and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p.) before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices) before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold), prefrontal (1.3 fold) and perirhinal (1.3 fold) cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold) from drug-treated rats (except for milrinone+RS 67333 treatment). After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold) and the perirhinal cortex (2.1 fold) from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold) and milrinone (respectively 1.46 fold and 1.56 fold)-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h).

Conclusions

Our results strongly suggest that a “pre-sample” early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.     

Effects of adrenocorticotropic hormone and dexamethasone on adrenal and hepatic alpha-tocopherol concentrations

Studies were done to determine the effects of ACTH treatment on adrenal alpha-tocopherol (alpha-T) concentrations in female rats. Administration of dexamethasone (DEX) to inhibit endogenous ACTH secretion increased whole adrenal alpha-T levels as well as the fractional amount in adrenal cytosol. Adrenal ascorbic acid (AA) concentrations were unaffected by DEX. DEX treatment also had no effect on hepatic AA content but decreased alpha-T concentrations in the liver. The subcellular distribution of alpha-T in the liver was not altered by DEX. Administration of ACTH to DEX-treated animals decreased adrenal alpha-T content and restored the pattern of subcellular distribution to that seen in controls. ACTH had no effect on hepatic alpha-T concentrations or subcellular distribution. ACTH treatment also had no effect on AA concentrations in adrenals or livers. The results demonstrate that ACTH has a role in the regulation of adrenal alpha-T but the mechanism(s) involved remain to be determined. The data also indicate that glucocorticoids such as DEX directly influence hepatic alpha-T levels independent of their effects on ACTH secretion.     

Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis

28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a ¹H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO?+?vehicle; MCAO?+?B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.