Farouk El-Sabban

Local cerebral hyperthermia induces spontaneous thrombosis and arteriolar constriction in the pia mater of the mouse

The effect of local cerebral hyperthermia on responses of pial microvessels of the mouse was investigated. A set protocol was followed, involving the performance of a craniotomy on anaesthetized animals and using intravital microscope-television closed circuitry. Controlled hyperthermic exposure was applied regionally by heating the brain surface with irrigating artificial cerebrospinal fluid. Microvascular responses such as changes in diameter, thrombosis and embolism were monitored and video-taped observations were further viewed and analysed. When both brain surface and core body temperatures were kept at 37° C, no changes in pial microvessels were noted. With core body temperature kept at 37° C and at a brain surface temperature of 43.1° C, passing emboli and arteriolar constriction were observed. A few minutes later, visible thrombosis was prevalent. Further spontaneous thrombo-embolic activity continued and at the end of a 50-min hyperthermic exposure, arterioles attained a constriction of 37%. Thrombus formation was sometimes massive enough to occlude fully the microvessel. The protocol followed in this study can be adopted to other small animal species and for a variety of experimental procedures involving hyperthermia and the pial microcirculation.

Lead alters structure and function of mouse flexor muscle.

To evaluate the effect of long‐term exposure to heavy metals on skeletal muscle, chronic subcutaneous injections for 7 days of two level treatments (low dose, 0.1 mg/kg and high dose, 1 mg/kg) of lead acetate were investigated. Comparative analyses of in situ dorsiflexor muscle isometric contractile characteristics were studied in urethane‐anesthetized (2 mg/g, i.p.) control and lead‐exposed male mice. Control muscle‐twitch tension reached an average of 1.81 ± 0.06 g. Chronic lead (Pb2+) treatments did not affect muscle contractile speed, but reduced significantly the twitch tension in both high and low doses when compared to control animals. This effect was in a dose‐dependent manner; 1.21 ± 0.07 g for low dose and 0.90 ± 0.05 g for high dose. These chronic Pb2+ treatments accelerated muscle fatigue after 250 stimuli (25 Hz for 10 sec) in both the low and high doses equally. However, marked elevation in tetanic (25 Hz) specific tension were observed in the high‐dose, chronically treated animals, indicating some changes in contractile apparatus function. The high dose of chronic Pb2+ treatment induced ultrastructural changes, including reduced number of synaptic vesicles, disruption of mitochondria and increased number of smooth endoplasmic reticulum and myelin‐like figures in the intramuscular axons and neuromuscular junctions. Chronic Pb2+ treatment caused extensive disruption of the sarcoplasmic mitochondria and increased the number of myelin‐like figures in the muscle. These results suggest that exposure to Pb2+ at a low concentration can compromise the in situ skeletal muscle isometric contraction.

Dehydration and food deprivation exacerbate mouse cerebral microvascular responses to local hyperthermia

Abstract 1. 1. Effects of 1-day deprivation from water, food or both on responses of mice pial microvessels to local cerebral hyperthermia were compared to fed mice and with access to water. 2. 2. A set of protocol for all groups was followed, which involved microsurgery and utilized intravital videomicroscopy. Core body temperature was kept at 37°C and hyperthermic exposure was applied locally by heating the artificial cerebrospinal fluid irrigating the brain surface, at 45°C for 25 min. 3. 3. Monitored responses included intravascular thrombo-embolic events and changes in microvascular diameter. Dehydration and food deprivation shortened the time for appearance of passing emboli and lowered the thermal threshold at which thrombo-embolic processes occur. 4. 4. Arteriolar constriction was observed in all groups, coupled with full occlusion. 5. 5. Data of this study revealed that dehydration and food deprivation exacerbate pial microcirculatory responses to local hyperthermia.

Neuromuscular and Microvascular Changes Associated with Chronic Administration of an Extract of Teucrium stocksianum in Mice

This work examines the effect on the weights of vital body organs, on blood biochemical variables, on neuromuscular coordination and on cerebral microcirculation of aqueous extracts of Teucrium stocksianum, given to mice in drinking water at concentrations of 2 and 4% for 56 days.

Aspirin influences mouse pial microvascular responses to regional hyperthermia

Abstract Pial microvascular responses to a hyperthermic exposure, at 44°C for 45 min, applied to the brain surface of anesthetized mice were observed and recorded by intravital videomicroscopy. The hyperthermic exposure was applied by heated artificial cerebrospinal fluid (ACSF). The effect of aspirin (100 mg/kg, i.p.), given 60 min prior to hyperthermic exposure was also studied. Mice were anesthetized (urethane, 1–2 mg/g, i.p.), the trachea was intubated and a craniotomy was performed. A cranial well was affixed on the animals head, to which ACSF was delivered and drained. Microvascular responses such as changes in diameter, thrombosis and embolism were monitored. With core body temperature kept at 37°C and at a brain surface temperature of 43.3 ± 1.0°C, passing emboli were first observed in arterioles and then shortly afterwards in venules. A few minutes later, visible thrombi were prevalent. Arteriolar constriction was also noted. Further thrombo-embolic activity continued and by the end of a 45-min exposure arterioles attained a 21% constriction. Aspirin, compared to control, delayed the appearance of the first observable response (18.6 ± 4.2 vs 11.5 ± 4.5 min, P P

Garlic prevents ultrastructural alterations caused by dehydration in mouse cerebral microvessels

Dehydration is known to significantly reduce both the time required for the first platelet aggregate and the time to full occlusion in photochemically‐induced thrombosis, in vivo. Ultrastructural changes that contribute to such events remain unknown. Therefore, the effect of water deprivation for 24 hr, (as a model for dehydration) on the ultrastructure of mouse pial microvessels was investigated. The possible beneficial effect of garlic in preventing such ultrastructural changes was also investigated. Four groups of TO strain: control, control‐garlic treated, dehydrated, and dehydrated‐garlic treated male mice, 10/group, were used. Dehydration was induced by water deprivation for 24 hr. Garlic solution was i.p. injected at 0.1 ml/10g body weight. In urethane‐anesthetized (2 mg/g, i.p.) mice, topical and transvessel bimodal fixation of pial microvessels was done with a phosphate buffered mixture of glutaraldehyde and paraformaldehyde, followed by a conventional electron microscopy procedure. Examination of control cerebral pial microvessels showed no evidence of cellular damage. Membranes of endothelial cells were intact. Within pial microvessels there was no evidence of platelet aggregation. Garlic treatments did not cause any ultrastructure abnormalities in control mice. Compared with control, dehydration caused the appearance of thrombi that consisted of platelet aggregates. Discoid platelets containing granules, spheroid degranulated platelets, and those with large pseudopodia were present in 80% of dehydrated mice. The venular endothelial surface of dehydrated mice revealed dilated profiles of endoplasmic reticulum and variously shaped vacuoles. Swelling of nuclear envelopes and mitochondrial distension were also present in dehydrated mice. Concomitant garlic treatment prevented most of these ultrastructural changes. These findings demonstrated the extent of damage to the pial microvessels in response to water deprivation and demonstrated the beneficial effect of garlic as a possible mean of protection against oncoming vascular pathology. Anat Rec 263:85–90, 2001.