Chronic cerebral hypoperfusion in male rats results in sustained HPA activation, and hyperinsulinemia

Vascular contributions to cognitive impairment and dementia (VCID) is a spectrum of cognitive deficits caused by cerebrovascular disease, for which insulin resistance is a major risk factor. A major cause of VCID is chronic cerebral hypoperfusion (CCH). Under stress, sustained hypothalamic-pituitary-adrenal axis (HPA) activation can result in insulin resistance. Little is known about the effects of CCH on the HPA axis. We hypothesized that CCH causes sustained HPA activation and insulin resistance. Male rats were subjected to bilateral carotid artery stenosis (BCAS) for 12 weeks to induce CCH and VCID. BCAS reduced cerebral blood flow and caused memory impairment. Plasma adrenocorticotropic hormone was increased in the BCAS rats (117.2 ± 9.6 vs. 88.29 ± 9.1 pg/mL, BCAS vs. sham, p = 0.0236), as was corticosterone (220 ± 21 vs. 146 ± 18 ng/g feces, BCAS vs. sham, p = 0.0083). BCAS rats were hypoglycemic (68.1 ± 6.1 vs. 76.5± 5.9 mg/dL, BCAS vs. sham, p = 0.0072), with increased fasting insulin (481.6 ± 242.6 vs. 97.94± 40.02 pmol/L, BCAS vs. sham, p = 0.0003) indicating BCAS rats were insulin resistant (HOMA-IR:11.71 ± 6.47 vs. 2.62 ± 0.93; BCAS vs. control, p = 0.0008). Glucose tolerance tests revealed that BCAS rats had lower blood glucose AUCs than controls (250 ± 12 vs. 326 ± 20 mg/dL/h, BCAS vs. sham, p = 0.0075). These studies indicate that CCH causes sustained activation of the HPA and results in insulin resistance, a condition that is expected to worsen VCID.

Abstract P740: Late Effects of Bilateral Carotid Artery Stenosis in an Aged Mouse Model

Bilateral carotid artery stenosis (BCAS) or global hypoperfusion is an experimental model of vascular dementia known to effect cognition. Chronic global hypoperfusion increases astrogliosis within the cortex and hippocampus, leading to reduced cognition. It is unknown if global hypoperfusion leads to respiratory deficits that could contribute to cognitive decline. We hypothesized that chronic global hypoperfusion in cerebral blood flow will lead to brain stem gliosis, respiratory dysfunction and progressive cognitive impairment. Female C57Bl/6 mice aged 18 months underwent BCAS (n=8) or sham (n=8) surgery to investigate changes in respiration (frequency, tidal volume, apneas), cognition (y-maze-spatial working memory and fear conditioning-contextual working memory), and changes in cortical and brain stem astrogliosis. Results demonstrated BCAS mice had decreased respiratory frequency and apneas (p<0.05), decreased cognition in both spatial and contextual working memory (p<0.05), and increased astrogliosis (p<0.01) within the cortex and brain stem. To determine if increased astrogliosis within the cortex and brain stem contributes to changes in respiration and delayed cognitive deficits, we administered a TGF-β inhibitor (Gw788388 Hydrate) through an osmotic pump 7 days post-BCAS or sham surgery and followed the mice for 56 days post-surgery. Results demonstrated a reduction in periodic apneas (p<0.01), cognitive deficits (p<0.05), and amelioration in gliosis (p<0.01) when comparing BCAS and sham mice. In conclusion, this study demonstrated global hypoperfusion leads to disrupted respiratory function, late cognitive deficits, and increased brain stem gliosis, that can be rescued through administration of TGF-β inhibitor. Respiratory instability may contribute to post-stroke cognitive deficits, and could be a therapeutic target to improve outcomes in patients with vascular dementia.

Thrombolytic Therapy for Acute Bilateral Carotid Artery Occlusion

Context: Acute bilateral internal carotid artery occlusion is a rare condition which is frequently associated with prolonged coma or brain death. There is no consesus on which is the optimal therapy for this condition, although there are reports of clinical improvement after mechanical thrombectomy. We present a case report of a patient treated with intravenous thrombolytic therapy. Case Report: A 82 year-old woman with previous history of hypertension and coronary artery disease presented with seizures, followed by coma. There was no description of focal neurological deficit. On examination, patient was comatous, with decebrate posturing after painful stimulus, bilateral myosis, showed absent oculocephalic reflex and absent corneal reflex on the left eye. CT scan showed diffuse hypodensities on the frontal and parietal lobes and on the superior temporal lobes. CT angiography showed occlusion of the right internal carotid artery and of the left common carotid artery. The patient was treated with 72mg of IV alteplase within 4 hours after symptom onset. There was no improvement after 24 hours. A new CT scan showed infarction of all anterior circulation territory. Diagnosis of brain death was made after 48 hours. Conclusions: Acute bilateral carotid artery occlusion is usually associated with poor outcome despite treatment. Endovenous thrombolytic therapy did not lead to clinical improvement on the presented patient. There is limited data on the efficacy of IV thrombolysis and other recanalization therapies for acute bilateral carotid artery occlusion.

Rare case of bilateral carotid artery dissection presenting with Foix-Chavany-Marie syndrome

Carotid artery dissection is one of the most common causes of ischaemic stroke in young and middle-aged population. We report a case of bilateral carotid artery dissection presenting with opercular syndrome or Foix-Chavany-Marie syndrome. This 46-year-old obese and hypertensive man with a history of fall from bike 1 week prior, presented with sudden onset of anarthria, dysphagia and deviation of angle of mouth. His speech and dysphagia gradually improved over 10 days to normal, but he developed pseudobulbar affect and difficulty in calculations 4 weeks later. MRI showed acute infarcts in bilateral operculum. CT angiography showed dissection in bilateral cervical ICAs. He was managed conservatively with oral anticoagulation, given for 6 months. Probability of dissection must be considered in patients with a history of trauma or falls developing focal neurological deficits. To our knowledge, this is the first case report of bilateral ICA dissection presenting with Foix-Chavany-Marie syndrome.