Ronald F. Dodson

Acute tissue response to cerebral ischemia in the gerbil. An ultrastructural study.

The Mongolian gerbil, because of the uniqueness of the anatomical features of its circle of Willis, has become an increasingly useful model in the study of cerebrovascular disease. The present work defines acute changes at the ultrastructural level following ischemic insult. The pathomorphological responses include initial astrocytic involvement and, when the degree of insult is increased, a progression of morphological changes is evident in neuronal and other parenchymal elements. Animals with vessels occluded for more than 3 hr without neurological signs suggestive of ischemia exhibited limited perivascular edema. Contralateral changes (perivascular astrocytic) were observed in the basal ganglia at 24 hr in animals with neurological deficit. Astrocytic and basal ganglia susceptibility to ischemia was consistent with previous findings in primate models. An additional association was found in that limited edematous involvement could exist in animals without neurological deficit but neuronal changes were only present in animals with signs of ischemic neurological deficit.

Hyperlipidemic Neuropathy and Dementia

Mixed types of sensory and motor peripheral neuropathy and dementia occurred as neurological complications in patients with established type IV and type V hyperlipoproteinemia. These complications were remedial by control of the hyperlipoproteinemia with diet and/or clofibrate resulting in symptomatic improvement as well as restitution of nerve conduction velocities toward normal. Diabetes mellitus as well as systemic metabolic and toxic disorders which commonly produce neurological complications were excluded. Segmental demyelination with disorganization of myelin lamellae were striking morphological features found on sural nerve biopsy. Fluctuations in memory performance correlated inversely with plasma lipid levels and appear to be a characteristic feature of hyperlipidemic dementia. Hyperlipidemic neuropathy and dementia, although rare, are remediable neurological disorders which should be considered in patients with neuropathy and/or dementia of unknown origin.

Acute Cerebral Infarction and Hypotension: An Ultrastructural Study

A comparison was made of morphological changes in brain tissue following periods of hypotension plus ischemia (due to occlusion of the middle cerebral artery) with those changes resulting from ischemia alone. It was found that a greater degree of swelling was present in the brains of those animals subjected to hypotension and ischemia than in those with vascular occlusion only. The type of organellular response in the hypotensive/ischemic animals was one of vacuolar formation within mitochondrial, endoplasmic reticular, and Golgi elements. It is concluded that the compound effects of hypotension plus ischemia result in more widespread and complex morphological response than either hypotension or ischemia alone. These morphological findings offer supportive data which will be further correlated with a future report on comparable changes in cerebral metabolism and hemodynamics.

Mitochondrial abnormalities in progressive external ophthalmoplegia.

Three cases of chronic progressive external ophthalmoplegia demonstrated ragged-red fibers. Histochemical stains showed that the ragged-red fiber appearance was produced by abnormal mitochondria in the muscle. Electron microscopic studies demonstrated the ultrastructural origin of the intramitochondrial inclusions seen in ragged-red fibers. The associated abnormalities in lactic acid metabolism possibly represent an underlying generalized defect in metabolism. This evidence suggests that chronic progressive external ophthalmoplegia is a diffuse disease of the mitochondria.

Acute Ultrastructural Changes in the Middle Cerebral Artery Due to the Injury and Ischemia of Surgical Clamping

Ultrastructural changes in the zone of clamping of the middle cerebral artery of the squirrel monkey are described after application of a surgical clip. The experimental model utilized has been widely applied to the study of cerebral ischemia and possibly has relevance to clamps applied to the cerebral vessels during neurosurgical treatment of patients with cerebrovascular disorders. The earliest changes within the arterial wall were found in the smooth muscle (media) and accompanying fasciculi of nerves. Changes within the nerve bundles were sufficiently advances following 4 hours of vascular clipping to suggest temporary or permanent impairment of neurogenic innervation of the cerebral vessels distal to the trunk of the vessel clipped.

The effects of glycerol on cerebral ultrastructure following experimentally induced cerebral ischemia

Ultrastructural changes in cerebral tissue subjected to temporary occlusion on the right middle cerebral artery for intervals of 30 min, 1, 2, 3, and 4 hr were studied after daily injections of 10% glycerol in saline. These changes were compared with previously reported data from untreated animals. The extent of tissue involvement was appreciably less in the glycerol-treated group as evidenced by the reduction of intracellular edema and fewer changes in the membranes of ultrastructural elements (mitochondria, endoplasmic reticulum, Golgi complex, and plasmalemma) known to be essential for cellular metabolism and function in the central nervous system.

Brain Tissue Pressure Gradients in Experimental Infarction Recorded by Multiple Wick-Type Transducers1

The wick catheter, applied to brain tissue pressure measurements by BROCK (1), appears to be a reliable device to measure the regional brain tissue pressure, based on our experience of implantation of about 150 wicks in 55 experimental animals.

Morphological responses of cerebral tissues to temporary ischemia.

The ultrastructural responses of cerebral tissue following temporary periods (1/2, 1,2,3, or 4 hour) of right, middle cerebral artery, (MCA) occlusion were studied acutely after a 3 day or 7 day interval following the removal of the MCA clip. Cortical and basal ganglia tissues for each ischemic duration were compared at 3 post-occlusive periods (acute, 3 days, 7 days). With the short periods of ischemic insult (1/2, 1, 2, 3, and 4 hour), the temporal and insular cortex contained no greater changes in the 7 day group than in the 3 day group. The basal ganglia were more susceptible to MCA occlusion as indicated by more marked cytological changes and/or necrosis in all intervals of ischemia.

The effect of glycerol and intracarotid phenoxybenzamine after experimental subarachnoid hemorrhage an ultrastructural study

SummaryTwenty-four hours and one week, respectively, after subarachnoid hemorrhage (SAH) had been experimentally induced in baboons, therapeutic dosages of glycerol and/or phenoxybenzamine hydrochloride were injected intravenously. Groups of three animals were studied at various time intervals after SAH: one animal served as a control, one animal per group received phenoxybenzamine hydrochloride (PBZ), and thefinal animal received both PBZ and a 10% glycerol (in saline) injection. The animals were prepared for electron microscopy by whole body perfusion with a glutaraldehyde/phosphate fixative.Few ultrastructural abnormalities were noted in cerebral tissue in each of the animals receiving glycerol, whereas the brain tissue from the untreated animals and those which had been treated with PBZ alone showed morphological changes compatible with cerebral edema.

Regional Cerebral Blood Flow Measured by the Gamma Camera After Direct Injection of 133Xe into the Distal Stump of the Occluded Middle Cerebral Artery

Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xe concurrently with measurements of local cerebral blood flow (LCBF) after injection of 133Xe directly into the distal stump of the occluded middle cerebral artery (MCA) by the use of the gamma camera after producing experimental ischemia in baboons by occluding the MCA. Regional MCA stump pressure (rMCAP) was also measured. Regions of ischemia assessed by intracarotid injection of 133Xe correlated well with the territory of infarct defined by injection of 133Xe into the distal MCA stump. Flow values in ischemic regions obtained by direct injection of 133Xe into the MCA were 15% to 20% lower than those obtained by intracarotid injection of 133Xe. Possible explanations for these differences are discussed. During induced hypertension autoregulation in ischemic areas was abolished and paradoxical responses of LCBF and rMCAP to changes in arterial carbon dioxide tension (Paco2) were confirmed.