Background: Ketamine is N-methyl-D-aspartate (NMDA) receptors blocking drug, it affects the cerebral cortex and play an essential role in learning and memory. Amyloid β (Aβ) is a cleavage product of a large, trans-membrane protein, termed amyloid precursor protein (APP); it may have a role in controlling synaptic activity. Objective: To investigate the immunohistochemical beta APP reaction in newborn mice frontal and parietal cerebral cortices after prenatal exposure to therapeutic doses of ketamine as an attempt for scientific judgments of making better understanding for effects of ketamine on developing brain, which may help to reduce adverse effects. Methods: Thirty pregnant mice were divided into two groups named experimental and control groups (15 mice for each groups). The experimental group animals were injected intraperitoneally with 50 mg/kg ketamine, the control group animals were injected with intraperitoneal distilled water. Paraffin sections of newborn mice frontal and parietal cortices were stained immunohistochmically with anti-APP antibodies. Results: The immunohistochemical labeling in the experimental group showed scattered clumps of brown staining distributed randomly in the cerebral cortex. The brown stained deposits vary also in shape and size, the larger and more intense staining was seen in the more superficial layers of the frontal cortex. The statistical analysis found non-significant differences in staining pattern between frontal and parietal cortices of control group, while significant differences were found between frontal and parietal cortices in experimental group. Conclusion: The immunohistochemical APP reactivity showed different intensities and different morphology in the frontal and parietal cortices in the all experimental group animals were that injected with ketamine in this study. These differences could be related to the requirement of this substance in repair and differentiation of the developing NMDA dependent interneuron impaired by prenatal ketamine exposure. Keywords: Frontal cortex, parietal cortex, amyloid precursor proteins, ketamine, prenatal, immnuohistochemistry Citation: Najm MS, Mubarak HJ, Mohammed LH. Amyloid precursor protein immunohistochemical changes in the newborn mice frontal and parietal cerebral cortices affected by prenatal exposure to ketamine. Iraqi JMS. 2018; 16(2): 191-200. doi: 10.22578/IJMS.16.2.11

Background: Ketamine is an N-methyl-D-aspartate (NMDA) receptor blocking agent, which is used for induction and maintenance of anesthesia. It affects the cerebral cortex and has an impact on learning and memory functions; suggesting that any changes in NMDA receptors function will have an adverse outcome on learning and memory abilities. Objective: To assess the histological changes in the frontal and parietal cortices of mice offspring’s after prenatal exposure to therapeutic doses of ketamine. Methods: Thirty pregnant mice were included in this study. They were divided into two groups named experimental and control groups (15 mice for each group). Those of experimental group were injected intraperitoneally with ketamine in a dose of 50 mg/kg/day on the 5th, 10th, 15th and 20th days of gestational age to showing effect of the ketamine after injection of it in all trimesters of pregnancy, while those of the control group were injected with distal water only with the same volume. The paraffin block sections of frontal and parietal cerebral cortices of newborn mice were stained by nissl stain. Results: In the control group, the mean number of Nissl stained cells in the frontal cortex showed a statistically significant increase compared to that of parietal cortex, while statistical non-significant decrease in the mean number of nissel stained cells of frontal cortex compared to that of parietal cortex. Conclusion: Iatrogenic apoptotic changes were seen in the cerebral cortex of the experimental mice after prenatal exposure to ketamine and it is more considerable in the frontal cortex than the parietal cortex. Keywords: Frontal cortex, parietal cortex, ketamine, nissl stain, development Citation: Najm MS, Mubarak HJ, Jarullah HA. Nissl stain expression in the frontal and parietal cortices of the newborn mice after prenatal exposure to ketamine. Iraqi JMS. 2018; 16(3): 268-278. doi: 10.22578/IJMS.16.3.6

Background: The vertebrate limb bud develops as an outgrowth of mesoderm, which forms all their elements (muscles, nerves, vessels, bone, cartilage, and tendon). Myogenic precursor cells are seen at E11.5 mouse embryo, when the first nerve fascicles begin to enter the limb. The first signs of musculature masses are seen at E12.5 in both fore and hind limb buds. Apoptosis or programmed cell death is essential in the development of the limbs. In vertebrate, the developing limb morphogenesis depends on the appropriate spatial and temporal balance between cell death and cell proliferation. Objective: To perform comprehensive analysis of the proximo-distal pattern of cell death, evaluated by (TUNEL test) in cross sections of mouse limbs during prenatal development after onset of primary myogenesis. Methods: Fifteen pregnant female mice (Musmusculus) were divided into three groups according to the days of pregnancy into day (14, 16 and 19), only two embryos were taken from each mouse. All the limb buds were involved in this study. Paraffin embedded histological cross-sections of the limb buds were prepared, histological staining (using H&E stain) and TUNEL test labeling were done. Assessment of the number of apoptotic cells in the limb bud mesenchyme was done by counting these cells. Results: The H&E stained sections of the limb buds showed less amounts of mesenchymal tissues in older embryos (day 19). The TUNEL stain showed active apoptotic changes at proximal parts of the limb buds at gestational day 19, while the distal parts of the limbs buds showed active apoptotic changes at the early days (day 14). The evaluation of TUNEL test reaction in the proximal regions showed statistical significant increase of apoptotic cells in day 19 compared to day 14 (p = 0.001 for both). The mean number of apoptotic cells in the proximal regions were statistically significant (p = 0.001) between day 16 and day 19. While the mean number of apoptotic cells of distal regions of the limb buds was higher at day 14 compared to that of day 16 and day 19. These differences between day 14 and day 16 were statistically significant and between day 16 and day 19 while statistically non-significant between day 14 and day 19. Comparison of mean number of apoptotic cells between proximal and distal regions in all the three groups showed a statistically significant higher mean number of apoptotic cells in the distal regions compared to proximal region (p = 0.001). The mean number of the apoptotic cells in both regions (proximal and distal) of the limb buds revealed statistically significant differences between day 16 and day 19 (p = 0.001). Conclusion: Apoptosis was higher in all parts of the developing limbs during day 19, and that could be associated with degenerative changes occurring at the apical ectodermal ridge. Moreover, apoptosis was higher in the distal part of the limb bud and this may be due to more differentiation of the distal parts than in the proximal part of the limb bud. Keywords: Development, limb bud, mouse, embryo, TUNEL, apoptosis, mesenchyme Citation: Al-Musawi DML, Mubarak HJ. Mesenchymal Cell death in mouse limb bud after the onset of primary myogenesis. Iraqi JMS. 2018; Vol. 16(1): 41-50. doi: 10.22578/IJMS.16.1.7

Many of the human anatomists wouldn't expect to discover a new body part, however, researchers claim that they found a network of fluid-filled spaces in connective tissues all over the body that hadn't been seen before and it acts like an "open, fluid-filled highway" that is supported by a lattice of thick collagen "bundles". The researchers stated that tissue fixation during the procedure of histological tissue processing causes collapse of this network of fluid-filled spaces, and these spaces were not seen during light microscopic examination till the new imaging technique were developed to allow examination of living tissues on a microscopic level. Keywords: Interstitium, anatomy, neworgan, cancer Citation: Mubarak HJ. The Interstitium (the pre-lymphatic region), is it a newfound 'organ'. Iraqi JMS. 2018; 16(3): 230-231. doi: 10.22578/IJMS.16.3.1