Entire Middle Cerebral Artery Territory Research Articles

Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study

AimsDexmedetomidine (Dex) has been noted to have neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the effect of Dex in diabetic hyperglycemia-exacerbated cerebral I/R injury and its underlying mechanism remain unclear. Main methodsThe infarct volume and brain edema were evaluated by 2,3,5-triphenyltetrazolium chloride staining and standard wet-dry method. Modified neurological severity score was utilized to assess the neurological deficits. The oxidative stress and inflammation were evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and cell count kit-8 were applied to measure cell apoptosis and viability. Key findingsDex treatment reduced infarct volume, decreased brain water content and improved neurological deficit in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Dex treatment reduced the levels of ROS, MDA, TNF-α and IL-1β in the entire middle cerebral artery territory of diabetic mice subjected to MCAO/R, as well as in primary culture of mouse hippocampal neurons stimulated with 50 mM glucose and oxygen glucose deprivation/reperfusion. Dex treatment inhibited neuronal apoptosis induced by diabetic hyperglycemia-exacerbated cerebral I/R injury. Dex upregulated nuclear factor of activated T-cells 5 (NFAT5) and Sirtuin 1 (SIRT1) expression, induced NF-E2-related factor 2 (Nrf2) translocation from cytoplasm to nucleus and inhibited the acetylation of Nrf2. However, these changes triggered by Dex treatment were abrogated by NFAT5 knockdown. SignificanceDex protects against diabetic hyperglycemia-exacerbated cerebral I/R injury through attenuation of oxidative stress, inflammation and apoptosis. The underlying mechanism is at least the NFAT5/SIRT1/Nrf2 signaling pathway dependent.

Abstract WP171: Hemodynamic Compromise Identified by Oxygen Extraction Fraction Response (OEFR) to Acetazolamide in Stroke Patients With Large Vessel Occlusion

Hemodynamic compromise identified by cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) in stroke patients with large artery occlusion is an independent predictor of stroke risk ranging from 27 to 57%. However, comparison of both methods indicates that the sensitivity of CVR is substantially greater than OEF in detecting hemodynamic compromise which may be because CVR includes a vasodilator challenge with acetazolamide as opposed to OEF made in the resting state. We hypothesized that the response of OEF (OEFR) to an acetazolamide challenge would better correlate with CVR than OEF. We examined the correlation between CVR and OEFR to acetazolamide in stroke patients with large artery occlusion. Methods: Stroke patients with large artery occlusion (internal carotid or middle cerebral artery) were studied by positron emission tomography (PET) using H2 15O2 (water) for cerebral blood flow (CBF) and 15O2 (gas) for cerebral metabolic rate for oxygen before and after acetazolamide. CVR was calculated as: CVR (%) = [(CBFa- CBFb)/CBFb] X 100; where: CBFb = CBF before acetazolamide, CBFa = CBF after acetazolamide. OEF response (OEFR) was similarly calculated as: OEFR (%) = [(OEFa-OEFb)/OEFb]X100; for the entire middle cerebral artery territory of each hemisphere. Results: There was a highly significant (P=0.0001) negative linear correlation between CVR and OEFR indicating increasing ischemic stress (Figure). Hemispheres from three patients showed a positive OEFR. Discussion: A positive OEFR in response to a cerebrovascular challenge definitively indicates hemodynamic compromise and eliminates the problem of deciding on the absolute threshold for OEF to signify hemodynamic compromise. A negative OEFR reflects sufficient cerebrovascular reserve relative to oxygen demand.

Decompressive craniectomy for severe middle cerebral artery infarction: a meta-analysis of randomised controlled trials

BackgroundSevere middle cerebral artery infarction is defined as an acute infarction in the entire middle cerebral artery territory. Several case series have indicated that decompressive hemicraniectomy for severe middle cerebral artery infarction is lifesaving. However, data concerning the long-term functional outcome are insufficient. We did a systematic review and meta-analysis to assess the efficacy of decompressive hemicraniectomy for patients with severe middle cerebral artery infarction. MethodsAccording to PRISMA guidelines, we searched databases containing articles published in English (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials CENTRAL) and Chinese (Chinese Biomedical Literature Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure) for randomised controlled trials (RCTs) of decompressive hemicraniectomy published before January, 2016. We extracted data on patient characteristics, methodological quality, and outcome measures. The outcomes assessed included mortality and good functional outcome (GFO). We did a subgroup analysis to determine the effect of age and surgical timing on mortality and functional outcomes. Findings14 studies were included in this meta-analysis, including 830 patients with severe middle cerebral artery infarction. In the total population, mortality was lower in the decompressive hemicraniectomy group than in the conventional treatment group at 6 months after onset (odds ratio [OR] 0·19, 95% CI 0·11–0·33; p<0·0001), and at 12 months (OR 0·18, 0·11–0·28; p<0·0001). The pooled OR of GFO was 3·15 (95% CI 1·49–6·69; p=0·003) at 6 months, and 1·95 (1·19–3·19; p=0·008) at 12 months. Survival with moderately severe disability was higher in the decompressive hemicraniectomy group at 6 months (OR 3·90, 95% CI 2·23–6·83; p<0·0001) and 12 months (OR 4·36, 2·55–7·36; p<0·0001). However, with regard to survival with severe disability, no significant differences were observed (p=0·55 at 6 months, p=0·81 at 12 months). In the subgroup analysis, compared with conventional treatment, decompressive hemicraniectomy significantly decreased mortality in patients older than 60 years (p<0·0001) and 60 years or younger (p<0·0001). With regard to survival with moderately severe or severe disability, significant differences were observed between treatment groups both in patients older than 60 years (p=0·0002) and 60 years or younger (p=0·0002). No significant differences between treatment groups were found in the subgroup analysis of surgical timing. InterpretationCompared with conventional treatment, decompressive hemicraniectomy could significantly reduce mortality and improve prognosis both in patients older than 60 years and those aged 60 years or younger with severe middle cerebral artery infarction. However, compared with conventional treatment, more patients who receive decompressive hemicraniectomy might survive with moderately severe or severe disability. FundingNone.

Neuroimaging patterns of ischemic stroke after percutaneous coronary intervention

We sought to determine neuroimaging patterns, ischemic mechanisms, and functional outcomes of ischemic stroke related to percutaneous coronary intervention (PCI) over a 16-year period. Stroke is a feared complication of PCI, associated with poor patient outcomes. The majority of strokes that occur after PCI are ischemic rather than hemorrhagic. However, mechanisms of cerebral ischemia in this setting are incompletely understood. We performed a retrospective single-center cohort study of patients with radiologically confirmed ischemic stroke occurring after PCI (PCI-stroke), between January 1, 1994 and December 31, 2009. Using brain imaging, infarctions were subclassified by radiological pattern and arterial territory as embolic, small subcortical, or hemodynamic. Modified Rankin Scale scores were used to assess functional outcome at 3 and 6 months. Radiologically confirmed PCI-stroke was identified in 35 patients. The majority of strokes (91%) revealed an embolic pattern, while the remaining strokes were small subcortical infarctions (9%). Watershed strokes with exclusive borderzone involvement, indicative of a hemodynamic mechanism, were not identified, despite the presence of periprocedural hypotension in 23% of patients. The middle cerebral artery (MCA) territory was affected most frequently (80%), and all patients suffering a complete MCA territorial infarction (14%) died in the hospital. Functional outcome among survivors of PCI-stroke was typically favorable in those who had single rather than multiple vascular territory involvement. The vast majority of radiologically confirmed ischemic strokes related to PCI are embolic. MCA territory strokes are most common and uniformly fatal when the entire MCA territory is affected. Functional outcomes in survivors of PCI-stroke are improved when only a single arterial territory is affected.

Recommendations for the Management of Cerebral and Cerebellar Infarction With Swelling

There are uncertainties surrounding the optimal management of patients with brain swelling after an ischemic stroke. Guidelines are needed on how to manage this major complication, how to provide the best comprehensive neurological and medical care, and how to best inform families facing complex decisions on surgical intervention in deteriorating patients. This scientific statement addresses the early approach to the patient with a swollen ischemic stroke in a cerebral or cerebellar hemisphere. The writing group used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. The panel reviewed the most relevant articles on adults through computerized searches of the medical literature using MEDLINE, EMBASE, and Web of Science through March 2013. The evidence is organized within the context of the American Heart Association framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive American Heart Association internal peer review. Clinical criteria are available for hemispheric (involving the entire middle cerebral artery territory or more) and cerebellar (involving the posterior inferior cerebellar artery or superior cerebellar artery) swelling caused by ischemic infarction. Clinical signs that signify deterioration in swollen supratentorial hemispheric ischemic stroke include new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size. In swollen cerebellar infarction, a decrease in level of consciousness occurs as a result of brainstem compression and therefore may include early loss of corneal reflexes and the development of miosis. Standardized definitions should be established to facilitate multicenter and population-based studies of incidence, prevalence, risk factors, and outcomes. Identification of patients at high risk for brain swelling should include clinical and neuroimaging data. If a full resuscitative status is warranted in a patient with a large territorial stroke, admission to a unit with neurological monitoring capabilities is needed. These patients are best admitted to intensive care or stroke units attended by skilled and experienced physicians such as neurointensivists or vascular neurologists. Complex medical care includes airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure monitoring or cerebrospinal fluid diversion is not indicated, but decompressive craniectomy with dural expansion should be considered in patients who continue to deteriorate neurologically. There is uncertainty about the efficacy of decompressive craniectomy in patients ≥60 years of age. In swollen cerebellar stroke, suboccipital craniectomy with dural expansion should be performed in patients who deteriorate neurologically. Ventriculostomy to relieve obstructive hydrocephalus after a cerebellar infarct should be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar displacement. In swollen hemispheric supratentorial infarcts, outcome can be satisfactory, but one should anticipate that one third of patients will be severely disabled and fully dependent on care even after decompressive craniectomy. Surgery after a cerebellar infarct leads to acceptable functional outcome in most patients. Swollen cerebral and cerebellar infarcts are critical conditions that warrant immediate, specialized neurointensive care and often neurosurgical intervention. Decompressive craniectomy is a necessary option in many patients. Selected patients may benefit greatly from such an approach, and although disabled, they may be functionally independent.

High‐resolution spatial mapping of changes in the neurochemical profile after focal ischemia in mice

After ischemic stroke, the ischemic damage to brain tissue evolves over time and with an uneven spatial distribution. Early irreversible changes occur in the ischemic core, whereas, in the penumbra, which receives more collateral blood flow, the damage is more mild and delayed. A better characterization of the penumbra, irreversibly damaged and healthy tissues is needed to understand the mechanisms involved in tissue death. MRSI is a powerful tool for this task if the scan time can be decreased whilst maintaining high sensitivity. Therefore, we made improvements to a (1)H MRSI protocol to study middle cerebral artery occlusion in mice. The spatial distribution of changes in the neurochemical profile was investigated, with an effective spatial resolution of 1.4 μL, applying the protocol on a 14.1-T magnet. The acquired maps included the difficult-to-separate glutamate and glutamine resonances and, to our knowledge, the first mapping of metabolites γ-aminobutyric acid and glutathione in vivo, within a metabolite measurement time of 45 min. The maps were in excellent agreement with findings from single-voxel spectroscopy and offer spatial information at a scan time acceptable for most animal models. The metabolites measured differed with respect to the temporal evolution of their concentrations and the localization of these changes. Specifically, lactate and N-acetylaspartate concentration changes largely overlapped with the T(2)-hyperintense region visualized with MRI, whereas changes in cholines and glutathione affected the entire middle cerebral artery territory. Glutamine maps showed elevated levels in the ischemic striatum until 8 h after reperfusion, and until 24 h in cortical tissue, indicating differences in excitotoxic effects and secondary energy failure in these tissue types.

Very brief focal ischemia simulating transient ischemic attacks (TIAs) can injure brain and induce Hsp70 protein

This study examined very brief focal ischemia that simulates transient ischemic attacks (TIAs) that occur in humans. Adult rats were subjected to sham operations or 5 min, 10 min, or 2 h of middle cerebral artery (MCA) ischemia using the suture (thread) model. Hsp70 protein was induced 24 h, 48 h and 72 h later in neurons throughout the entire MCA territory in many but not all animals. Following 5- and 10-minute MCA occlusions, 9 of 32 animals (28%) had microinfarcts mostly in dorsal lateral striatum. Uncommon Hsp70 stained intracellular cytoplasmic inclusions, some of which co-localized with activated caspase-3, were detected in microglia, macrophages, astrocytes and oligodendrocytes. Hsp70 stained neurons were TUNEL negative at 24 h and 48 h whereas some Hsp70 stained neurons were TUNEL positive at 72 h after reperfusion. Hsp70 positive, activated “bushy” microglia and Hsp70 negative, activated “polarized” or rod-shaped microglia were located outside of the microinfarcts. Thus, experimental focal ischemia simulating TIAs can: induce Hsp70 protein throughout the ischemic vessel territory; produce Hsp70 protein positive glial inclusions; activate Hsp70 positive and negative microglia; and cause microinfarcts in some animals.

ｒｔ‐ＰＡ（アルテプラーゼ）静注療法施行例における頭蓋内出血の臨床的検討

Over an 18-month period, 511 patients with ischemic stroke were admitted to our hospital; 18 were treated with intravenous recombinant tissue plasminogen activator (rt-PA, alteplase 0.6mg/Kg). After rt-PA treatment, symptomatic intracranial hemorrhages (SIH) developed in 5 patients (age range, 58-85 years; time to treatment, 84-175 minutes; baseline NIHSS, 16-21); 3 had a hemorrhagic infarction; 1 had an intracranial hematoma; and 1 had a subarachnoid hemorrhage. Development of SIH related to NIHSS and antithrombotic medications. Three months after onset, their modified Rankin scale (mRS) scores were 2 in 1 patient and 5 in 4 patients. One patient had a cardioembolic stroke (CE) in the middle cerebral artery (MCA) territory that did not affect the perforating area and recovered functionally (mRS, 2), while 2 patients who had a CE in the entire MCA territory became bedridden (mRS, 5). In 2 patients not treated with anticoagulants, the hemorrhagic infarction kept enlarging until 2 weeks. In one patient who developed a subarachnoid hemorrhage after rt-PA, no aneurysms had been noted on MR angiography at the time of arrival. In conclusion, the risks and benefits of rt-PA need to be carefully considered in stroke patients, especially, those with severe neurological deficits.

Endovascular treatment of an “anterior cerebral artery” aneurysm in a patient with “embryonic unfused middle cerebral artery” anomaly: a case report

We report a unique case of an anterior cerebral artery aneurysm in a patient with embryonic unfused middle cerebral artery anomaly. The arterial twigs of the middle cerebral artery supply the entire middle cerebral artery territory including the lenticulostriate branches. There was a vessel incorporated into the aneurysm, which was referred to as an accessory middle cerebral artery and it gave rise to a lenticulostriate branch. The aneurysm was occluded with detachable coils using a remodeling technique. After successful occlusion of the aneurysm the so-called accessory middle cerebral artery including its lenticulostriate branch started to fill from the anomalous middle cerebral artery network and the patient did not experience any ischemic injury.

Imaging the ischemic penumbra with 18F-fluoromisonidazole in a rat model of ischemic stroke.

The ischemic penumbra is a major focus of stroke research. 18F-fluoromisonidazole (18F-FMISO), a positron emission tomography (PET) marker of hypoxic cells, has shown promise as a technique to image the penumbra in humans. Our aim was to delineate the pattern of 18F-FMISO binding in a rat middle cerebral artery transient thread-occlusion model, and correlate this with tissue outcome at 24 hours. We hypothesized that the pattern of 18F-FMISO binding would mimic that seen in humans. Thirty-eight rats underwent 2 hours transient middle cerebral artery (MCA) occlusion, and then received 18F-FMISO at time points from 0.5 to 22 hours post-MCA occlusion and were killed 2 hours later. Autoradiographic assessment of 18F-FMISO binding and assessment (triphenyltetrazolium chloride) of the area of infarction were performed on tissue slices. Until 1 hour after MCA occlusion, 18F-FMISO binding was increased in the entire MCA territory, with little or no infarction visible. Over the next 5 hours, the pattern of binding evolved to a small rim of intensely binding tissue surrounding the infarct core, which itself showed reduced binding compared with the contralateral hemisphere. By 24 hours, there was minimal accumulation of 18F-FMISO binding and a large area of infarction. The pattern of 18F-FMISO binding rats reproduced the pattern seen in humans, consistent with this tracer being a marker of the ischemic penumbra in both species. This technique may have application in studying the ischemic penumbra in animal models, and correlating this with similar studies in humans.

Early decrease in dna repair proteins, Ku70 and Ku86, and subsequent DNA fragmentation after transient focal cerebral ischemia in mice.

Ku70 and Ku86, multifunctional DNA repair proteins, bind to broken DNA ends, including double-strand breaks, and trigger a DNA repair pathway. To investigate the involvement of these proteins in DNA fragmentation after ischemia/reperfusion, Ku protein expression was examined before and after transient focal cerebral ischemia (FCI) in mice. Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal suture blockade of the middle cerebral artery. Ku protein expression was studied by immunohistochemistry and Western blot analysis. DNA fragmentation was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). The spatial relationship between Ku expression and DNA fragmentation was examined by double labeling with Ku and TUNEL after reperfusion. Immunohistochemistry showed constitutive expression of Ku proteins in control brains. The number of Ku-expressing cells was decreased in the entire middle cerebral artery territory as early as 4 hours after reperfusion and remained reduced until 24 hours. Western blot analyses confirmed the significant reduction of these proteins (59.4% and 57.7% reduction in optical density at 4 hours of reperfusion from the normal level of Ku70 and Ku86 bands, respectively; P<0.001). DNA gel electrophoresis demonstrated DNA laddering 24 hours after reperfusion, but not at 4 hours. Double staining with Ku and TUNEL showed a concomitant loss of Ku immunoreactivity and TUNEL-positive staining. These results suggest that the early reduction of Ku proteins and the loss of defense against DNA damage may underlie the mechanism of DNA fragmentation after FCI.

Early decrease of XRCC1, a DNA base excision repair protein, may contribute to DNA fragmentation after transient focal cerebral ischemia in mice.

DNA damage and the DNA repair mechanism are known to be involved in ischemia/reperfusion injury in the brain. The x-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after transient focal cerebral ischemia (FCI). Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal blockade of the middle cerebral artery. XRCC1 protein expression was analyzed by immunohistochemistry and Western blot analysis. DNA damage was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL). The spatial relationship between XRCC1 expression and DNA damage was examined by double staining with XRCC1 and TUNEL after FCI. Immunohistochemistry showed the nuclear expression of XRCC1 in all regions of the control brains and that it was predominant in the hippocampus. The XRCC1 level was markedly reduced in the caudate putamen at 10 minutes, further decreased in the entire middle cerebral artery territory at 1 hour, and remained reduced until 4 and 24 hours after FCI. Western blot analysis of the normal control brain showed a characteristic band of 70 kDa, which decreased after FCI. A significant amount of DNA fragmentation was detected by DNA gel electrophoresis 24 hours but not 4 hours after FCI. Double staining showed that the neurons that lost XRCC1 immunoreactivity became TUNEL positive. These results suggest that the early decrease of XRCC1 and the failure of the DNA repair mechanism may contribute, at least in part, to DNA fragmentation after FCI.

Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice.

The authors examined the protein expression of apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, before and after transient focal ischemia in mice. Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the entire region of the control brains. Nuclear immunoreactivity was decreased as early as 5 minutes after 60 minutes of ischemia in the ischemic core, which was followed by a significant reduction of APE/Ref-1-positive cells in the entire middle cerebral artery territory. Western blot analysis of the sample from the nonischemic brain showed a characteristic 37-kDa band, which was reduced after ischemia. A significant amount of DNA fragmentation was observed at 24 hours, but not at 4 hours, after ischemia. The authors' data provide the first evidence that APE/Ref-1 rapidly decreases after transient focal ischemia, and that this reduction precedes the peak of DNA fragmentation in the brain regions that are destined to show necrosis and apoptosis. Although further examination is necessary to elucidate the direct relationship between the APE/Ref-1 decrease and ischemic necrosis and apoptosis, our results suggest the possibility that rapid decrease of APE/Ref-1 and the failure of the DNA repair mechanism may contribute to necrosis or apoptosis after transient focal ischemia.

A reproducible model of thromboembolic stroke in mice.

AN experimental mouse model of thromboembolic stroke is presented, in which standardized fibrin-rich emboli (150 microm diameter, 1.5 mm or 4 mm length) are injected into the internal carotid artery. Injection of six or eight 1.5 mm clots (corresponding to 0.16 or 0.21 microl clot material) led to a variable decrease in laser Doppler flow (LDF), but did not result in reproducible infarcts of the middle cerebral artery (MCA) territory, as determined by triphenyltetrazolium chloride (TTC) staining 24 h after embolization. Injection of ten 1.5 mm clots (0.27 microl) or four 4 mm clots (0.28 microl), however, caused a persistent LDF decline to about 20-30% of baseline and led to reproducible infarcts covering the entire MCA territory. The method establishes a clinically relevant, reproducible stroke model for the study of molecular mechanisms of ischemic brain injury in genetically engineered mice.

Hemorrhagic infarct conversion in experimental stroke

This study investigated the relations between hemorrhagic infarction and occlusion, release, levels of glycemia, brain energy state, and lactate content after cerebrovascular occlusion. Prospective, controlled laboratory investigation. One hundred six pentobarbital-anesthetized cats. The middle cerebral artery was occluded with a Yasargil clip transorbitally either temporarily (0.5, four, and eight hours) or permanently. Normoglycemic and hyperglycemic animals were closely monitored for eight hours. Brain pathology was assessed after two weeks' survival or at the time of spontaneous animal death. Topographic brain metabolite studies were carried out after four hours of middle cerebral artery occlusion. Morphometric quantitation of cerebral hemorrhage and infarction and fluorometric determinations of blood and brain tissue, glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine from 16 topographic brain sites were carried out. Twenty-one of 82 (25.6%) animals evaluated neuropathologically showed hemorrhagic infarcts. Occluding the artery in hyperglycemic animals caused fivefold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Temporary occlusion with clip release after four hours in hyperglycemic animals caused the most extensive hemorrhage into infarcts. Most hemorrhages into infarcts (81%) took place in animals that died within a few hours after they experienced ischemia and that showed infarction and marked edema of the entire middle cerebral artery territory. Linear regression analyses demonstrated a close relation between hemorrhage into infarcts and near-total energy depletion (adenosine triphosphate, less than 0.3 microM/g; phosphocreatine, less than 0.5 microM/g) in brain sites that showed extremely high tissue lactate concentrations (more than 30 microM/g). The biochemical changes that correlated with hemorrhage into infarcts were more marked than those with infarcts without hemorrhage. Hyperglycemia and restoration of blood flow to ischemic territories were strong risk factors for hemorrhagic infarct conversion. Concomitant tissue metabolic changes suggest that marked tissue energy depletion accompanied by acidosis damages brain vessels and renders them penetrable for edema fluid and, ultimately, red blood cell extravasation.

Internal borderzone infarction following acute middle cerebral artery occlusion

In 36 patients suffering acute middle cerebral artery (MCA) occlusion, we studied the angiographic findings within 6 hours of the ictus and the chronic CT results at 3 months. Seven patients suffering distal pial MCA branch occlusion developed a pattern of internal borderzone infarction on follow-up CT. Carotid artery or carotid siphon stenosis or occlusion was absent in all seven. Proximal MCA branch occlusions, prior to the origin of the lenticulostriate arteries, were associated with extensive cortical and deep infarction in the entire MCA territory in 14 patients. There was proximal carotid artery or siphon stenosis or occlusion in 12 of these 14 patients. The remaining 15 patients showed a mixture of proximal and distal MCA occlusions and patchy ischemic damage in the MCA territory. There were no cases of superficial cortical watershed infarction. These data show that internal borderzone infarctions may result from intracranial MCA branch occlusions alone and need not be associated with hemodynamic alterations due to large vessel extracranial disease.

Effects of vasospasm in the middle cerebral artery territory on flow velocity and volume flow. A computersimulation.

Recently blood flow velocity in large cerebral arteries became measurable non-invasively by transcranial Doppler sonography (TCD). The present study tries to quantify the relation between flow velocity and the more important volume flow in the middle cerebral artery (MCA) by means of computersimulation. A mathematical model of the MCA territory was developed. The model is able to take into account the non-Newtonian behaviour of blood viscosity and is also able to handle turbulant and laminar flow. Autoregulation is simulated by increasing or decreasing diameter of arteries as an answer to intraluminal pressure changes. Two processes are simulated: Vasospasm in the stem of the MCA, and vasospasm in the entire MCA territory. Results show that the relation between flow velocity and volume flow is rather complicated. Vasospasm in the MCA stem first leads to an increase of flow velocity at a constant level of volume flow. At higher grades of vessel constriction volume flow and flow velocity start to fall.

Young adult stroke: neuropsychological dysfunction and recovery.

Etiology, neuropsychological deficits, aphasia type, and recovery were retrospectively studied in 254 young adults with stroke. Cardiac embolism was the most common cause of stroke in patients younger than 40, while atherosclerosis was the most frequent etiology among those aged 41-50 years. In 166 aphasic patients, Broca's aphasia was the most common while Wernicke's and transcortical aphasias were rare. Compared with an older aphasic population, young patients had significantly more nonfluent aphasias and fewer comprehension deficits. These differences were related to stroke localization: the majority of infarcts localized by computed tomography in 37 patients involved either the entire middle cerebral artery territory or its superior or deep branches, explaining the preponderance of nonfluent aphasia. Prognosis of aphasia in our patients was better than has been reported for non-age-selected aphasia populations. Roughly one third of our patients recovered completely, one third improved, and one third had an unresolved language deficit. Complete recovery and significant improvement were observed even greater than 6 months after stroke. In some patients, recovery was much better than might have been predicted from lesion site and size depicted on computed tomograms.

Hyperglycemia enlarges infarct size in cerebrovascular occlusion in cats.

We investigated the influence of serum glucose concentration on infarct size following middle cerebral artery occlusion in cats. These animals were deprived of food for 48 hours and infused with 1) saline for 1 hour before and 8 hours after occlusion (n = 8), 2) 10% glucose solution for 1 hour before and 6 hours after occlusion and saline for 2 additional hours (n = 8), or 3) 10% glucose for 1 hour before and saline for 8 hours after occlusion (n = 5). Nineteen cats killed after 2 weeks' survival were subjected to morphometric infarct size determinations. Eight normoglycemic and 11 hyperglycemic cats exhibited infarcts affecting 10.2 +/- 3.4% and 29.5 +/- 6.5% (mean +/- SEM) of their middle cerebral artery territories, respectively (p less than 0.02). Cats of the two hyperglycemic groups showed similarly sized infarcts. However, two of eight (25%) of cats with preocclusion and postocclusion hyperglycemia died 8 and 24 hours after occlusion with infarction of the entire middle cerebral artery territory, marked hemispheral edema, and brainstem compression. Our results demonstrate that serum glucose concentration at the time of large cerebral vessel occlusion influences stroke outcome.

Impaired microvascular filling after focal cerebral ischemia in monkeys.

✓ Impairment of microvascular filling was demonstrated in relation to focal cerebral ischemia in the monkey. Temporary or sustained middle cerebral artery (MCA) clipping was achieved with a microsurgical technique. Animals were sacrificed by perfusion with a carbon black suspension. Brains were fixed in formalin, and the extent of microvascular carbon filling was estimated grossly and microscopically. In most animals, MCA occlusion of 2 hours to 7 days produced diminished filling in small vessels in the MCA territory of supply. The impairment of filling was most pronounced in the deep subcortical structures but also affected the cortex in some animals. Temporary and sustained occlusion of equal duration produced roughly equivalent areas of abnormal filling. The impairment of vascular filling tended to be more extensive with increasing duration of occlusion. Hypotension during MCA occlusion caused almost total non-filling of the microvasculature in the entire MCA territory. Impaired filling of vascular channels may play a role in the pathogenesis of some clinical cerebrovascular diseases.