Magnetic resonance analysis of the effects of acute ammonia intoxication on rat brain. Role of NMDA receptors

Abstract

Acute ammonia intoxication leads to rapid death, which is prevented by blocking N-methyl-D-aspartate (NMDA) receptors. The subsequent mechanisms leading to death remain unclear. Brain edema seems an important step. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance and to assess which effects are mediated by NMDA receptors activation. To assess edema induction, we injected rats with ammonium acetate and measured apparent diffusion coefficient (ADC) in 16 brain areas. We also analyzed the effects on T1, T2, and T2* maps and whether these effects are prevented by blocking NMDA receptors. The effects of acute ammonia intoxication are different in different brain areas. T1 relaxation time is reduced in eight areas. T2 relaxation time is reduced only in ventral thalamus and globus pallidus. ADC values increased in hippocampus, caudateputamen, substantia nigra and cerebellar cortex, reflecting vasogenic edema. ADC decreased in hypothalamus, reflecting cytotoxic edema. Myo-inositol increased in cerebellum and substantia nigra, reflecting vasogenic edema. N-acetylaspartate decreased in cerebellum, reflecting neuronal damage. Changes in N-acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo-inositol (induction of edema) are not.

Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain

“…This agrees with a recent report (4) showing by magnetic resonance in vivo that acute ammonia intoxication in rats induces cerebral edema (changes in apparent diffusion coefficient and myoinositol levels), neuronal damage (changes in N-acetylaspartate), and changes in T1 and T2 in some brain areas. Changes in N-acetylaspartate, T1, and T2 are prevented by MK-801 whereas ammoniainduced edema (changes in apparent diffusion coefficient or myoinositol) is not prevented by blocking NMDA receptors with MK-801.…”

“…It is therefore likely that the high ammonia levels contribute to the process by which ALF leads to death. Acute ammonia intoxication affects different cerebral processes (11,24) and leads to activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptors in brain (13) and, subsequently, to oxidative stress (17), altered mitochondrial calcium homeostasis (19), depletion of ATP (16), proteolysis of microtubule-associated protein 2 and microtubule disaggregation (10), and neuronal damage (4).…”

Acute Hepatic Encephalopathy: Diffusion-Weighted and Fluid-Attenuated Inversion Recovery Findings, and Correlation with Plasma Ammonia Level and Clinical Outcome

“…For example, an experiment injecting rats with ammonium acetate noted ADC abnormalities in various regions, such as the thalami, caudate, putamen, and cerebellum, to name a few. 18 On positron-emission tomography, increased blood flow and nitrogen-13 ammonia uptake have been noted in the thalami, lentiform nucleus, and cerebellum in acute hepatic encephalopathy. 31 Notably, PALs have been shown to positively correlate with ADC values in the thalami, pallidi, putamen, and PVWM in patients with chronic hepatic failure.…”

“…17 Hence, FLAIR, T2WI, or DWI MR imaging could detect such regional abnormalities in patients with acute hepatic encephalopathy from AHF or ACHF. [12][13][14][15][16]18 Thus, because FLAIR and DWI are generally considered routine sequences for brain imaging in most institutions, these 2 sequences could be useful in determining characteristic regions of involvement. The current study was designed after noting changes on FLAIR and DWI sequences within the thalami and PLIC in 2 patients presenting with clinical symptoms of acute hepatic encephalopathy, who were part of a larger study evaluating involvement of the PVWM by toxic causes of acute leukoencephalopathy.…”

In vivo proton magnetic resonance spectroscopy for the evaluation of hepatic encephalopathy in dogs

“…[21][22][23][24][25][26][27][28] The use of 1 H MRS for the diagnosis and investigation of pathophysiologic mechanisms of hepatic encephalopathy in humans and other animals has been reported. 15,[29][30][31][32][33][34][35][36][37][38] The main finding in those studies was the increased glutamine-glutamate complex peak and reduced myoinositol peak, which reflect amino acid disturbances and osmoregulation, respectively. The use of 1 H MRS in veterinary medicine is not widespread.…”