Adjuvant-induced mono-arthritis potentiates cerebral hemorrhage in the spontaneously hypertensive rats

作者：Randell Amy; Daneshtalab Noriko^*

来源：Life Sciences, 2016, 151: 15-22.

DOI：10.1016/j.lfs.2016.02.012

• Rheumatoid arthritis
• Hypertension
• Spontaneously hypertensive rats
• High salt diet
• Hemorrhagic stroke
• Complete Freund's adjuvant
• Animal models
• Mono-arthritis
• Adjuvant-induced-arthritis

Aims: Patients with rheumatoid arthritis (RA), have a higher incidence of hypertension and stroke than the normal population. Currently there exists no animal model to study the pathogenic interactions of hemorrhagic stroke (HS) subsequent to chronic inflammation and hypertension. We have created and defined a hypertensive-mono-arthritic animal model who demonstrate gros signs of cerebral hemorrhage in presence of mono-arthritis.
Main methods: Spontaneously hypertensive rats (SHR) were fed either a high salt diet (4% NaCl; HSD) or Purina chow (RD) from weaning. Complete Freund's adjuvant (CFA) was injected into the left hind paw at 21-28 weeks (control groups received saline (SAL)). Degree of inflammation, joint swelling, weight and blood pressure were monitored for 21 days. Animals were then sacrificed and their brain and left hind paw evaluated.
Key findings: All groups were hypertensive throughout the experimental period (>180 mm Hg systolic), irrespective of diet. Both CFA groups produced significant local inflammatory response in their injected paw with associated joint degradation and cellular infiltrates. Systemic plasma TNF-alpha levels were significantly elevated in CFA groups, with significant increase in TNF-a at 7 and 14 days, compared to SAL groups. Cerebral hemorrhage was visualized in the CFA groups but not SAL controls, with a higher severity in HSD-CFA group.
Significance: Themono-arthritic hypertensive animals are capable of developing HS upon induction of inflammatory insult. The HSD appears to exacerbate the inflammatory response and influence degree of the hemorrhage. Our novel, multi-disease model may provide an appropriate platform to study the pathogenesis of HS among arthritic patients.

• 出版日期2016-4-15