Biomedical subjects

Mohamed T Khashaba

Publications and source records attributed to Mohamed T Khashaba.

3 recordsLinked to original sources

PubMed2006

Excitatory amino acids and magnesium sulfate in neonatal asphyxia.

OBJECTIVE: The excitatory amino acids (EAA); glutamate and aspartate are released into the cerebrospinal fluids (CSF) of asphyxiated newborns. The objectives of this study were: (a) to examine the relation of the concentration of EAA in the CSF with the degree of brain injury, (b) To determine the time of the release of these EAA into the CSF, and (c) to detect the effect of magnesium sulfate (MgSO(4)) on their levels. DESIGNS AND METHODS. A randomized controlled trial was conducted on 47 full term asphyxiated newborns. Twenty three infants received an intravenous 10% solution of MgSO(4) at a dose of 250 mg/kg within the first 24h of life while the other 24 newborns received isotonic saline (0.9%) of an equal volume. Levels of glutamate and aspartate were measured before and 72 h after giving the trial solution. Results. In the study population (n=47) both glutamate and aspartate were significantly elevated in infants with higher grades of HIE compared to those with lower grades (P=0.013 and 0.031, respectively). Compared to baseline level, glutamate decreased significantly over time in placebo group (-8.28+/-14.26, P=0.025) and in MgSO(4) group (-14.39+/-18.72, P=0.005). Glutamate concentration did not differ between groups when measured at baseline (29.26+/-16.31 vs. 31.27+/-22.62, P=0.82) and at 72 h (19.28+/-15.63 vs. 19.6+/-16.54, P=0.87). The change in aspartate concentration over time was not significant in placebo group (-0.45+/-1.96, P=0.34) or in MgSO(4) group (-0.7+/-3.19, P=0.37). Aspartate did not differ between groups when measured at baseline (3.52+/-2.4 vs. 3.92+/-2.59, P=0.49) or at 72 h (2.79+/-1.24 vs. 3.05+/-2.48, P=0.92). Conclusions. The EAA; glutamate and aspartate are released in the CSF of asphyxiated newborns immediately after birth and declined by 72 h. Their initial concentrations correlated with the severity of HIE. Postnatal administration of MgSO(4) did not alter the levels of these 2 EAA.

Anticonvulsants↗

PubMed2005

IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy.

The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates is not fully defined. We hypothesize that interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) correlate with the severity of brain injury and can predict neurological deficits in infants who suffered from hypoxic ischemic encephalopathy (HIE). A prospective study was conducted on 24 term infants diagnosed with HIE and 13 controls. HIE was clinically classified into mild, moderate and severe according to Sarnat and Sarnat grading. Blood and CSF samples were obtained from all infants in the first 24h of life as part of routine investigations for suspected meningitis and/or sepsis. Neurological examination and Denver Developmental Screening Test II (DDST II) were performed at 6 and 12 months of life. IL-1beta, IL-6 and TNF-alpha were all significantly increased in HIE infants when compared to control. IL-1beta in the CSF correlated with the severity of HIE (r=0.61, P=0.001) more than IL-6 (r=0.45, P=0.004) or TNF-alpha (r=0.47, P=0.003). IL-1beta exhibited the highest CSF/serum ratio among the three studied cytokines suggesting its local release in the brain after the initial hypoxic injury. Abnormal neurological findings and/or abnormal DDST II at 6 and 12 months were best predicted by IL-1beta in the CSF (sensitivity=88% and specificity=80%). This study confirms the role of IL-1beta in the ongoing neuronal injury that occurs in the latent phase following the original HIE insult.

Asphyxia Neonatorum↗

PubMed2005

Complement component 9 activation, consumption, and neuronal deposition in the post-hypoxic-ischemic central nervous system of human newborn infants.

The role of complement in neonatal hypoxic-ischemic brain injury is not known. Therefore, cerebral spinal fluid (CSF) and post-mortem cerebral tissue were analyzed to determine whether complement is activated and complement component 9 (C9) is deposited on neurons in the central nervous systems (CNS) of newborn infants who developed moderate to severe hypoxic-ischemic encephalopathy (HIE). Control CSF samples were obtained during routine evaluation for possible sepsis from infants who were not depressed at birth. In ELISA assays of CSF obtained from 16 infants with HIE, compared to CSF from 7 control infants, the mean concentration of terminal complement complexes was elevated and the mean C9 concentration was diminished. Immunofluorescence microscopy of post-mortem frozen brain tissue obtained from two infants who expired at 4-5 days of life after severe HIE revealed that activated C9 was deposited on cells in all lobes. Double label immunofluorescence microscopy demonstrated that nearly all of the C9-positive cells were neurons and essentially all of the neurons were C9-positive. Immunoperoxidase immunohistochemistry of formalin-fixed tissue also confirmed the presence of many C9-positive cells, particularly in the hippocampus. The C9-positive cells usually manifested morphology consistent with neurons, most of which contained fragmented nuclei. In summary, complement was activated in the CNS of newborn infants who developed moderate to severe HIE. C9 was deposited on neurons, including morphologically apoptotic neurons. Further investigations into a possible role of complement in the pathogenesis of neonatal hypoxic-ischemic cerebral injury are warranted.

Brain↗