Characterizing nerve response post renal denervation is the most critical aspect of any preclinical renal denervation study. Nerve atrophy, healing changes (fibrosis), condition of the perineurium, neuromatous regeneration; all of these aspects determine the success or failure of the denervation treatment.

We are honored to present our most recent publication: “Neuromatous Regeneration as a Nerve Response After Catheter-Based Renal Denervation Therapy in a Large Animal Model Immunohistochemical Study.”

This paper is the first preclinical testing documentation that a progressive regenerative response occurs as early as 7 days after renal denervation, resulting in a poorly organized neuromatous regeneration. This finding is of paramount importance to further establish the potential functional significance of regeneration after renal denervation.

T3 Labs’ Study Director Irena Brants, DVM, along with our longtime partners Alizee Pathology and other industry leaders in the field recently co-authored this paper in Circulation: Cardiovascular lnterventions. T3 Labs’ experience with this preclinical testing model is not just limited to execution, we are interested in understanding and participating in the science and methods behind this therapeutic option for resistant hypertension.

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ABSTRACT

NEUROMATOUS REGENERATION AS A NERVE RESPONSE AFTER CATHETER-BASED RENAL DENERVATION THERAPY IN A LARGE ANIMAL MODEL: IMMUNOHISTOCHEMICAL STUDY.

Rousselle SD1, Brants IK1, Sakaoka A1, Hubbard B1, Jackson ND1, Wicks JR1, Dillon KN1, Naiche LA1, Hart R1, Garza JA1, Tellez A2.

Author information:

  • 1From the Alizée Pathology, LLC, Thurmont, MD (S.D.R., N.D.J., J.R.W., K.N.D., L.A.N., R.H., J.A.G., A.T.); Translational Testing and Training (T3) Laboratories, Atlanta, GA (I.K.B., B.H.); and Terumo Corporation, Kanagawa, Japan (A.S.).
  • 2From the Alizée Pathology, LLC, Thurmont, MD (S.D.R., N.D.J., J.R.W., K.N.D., L.A.N., R.H., J.A.G., A.T.); Translational Testing and Training (T3) Laboratories, Atlanta, GA (I.K.B., B.H.); and Terumo Corporation, Kanagawa, Japan (A.S.). atellez@alizeepathology.com.

BACKGROUND:

Renal denervation (RDN) emerged as a therapeutic option for resistant hypertension. Nerve regrowth after RDN has been questioned. We aimed to characterize the nerve response after RDN.

METHODS AND RESULTS:

Swine underwent bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100 (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of necrosis associated with perineurial fibrosis and distal atrophy with inflammation. At 30 days changes were substituted by healing changes (ie, fibrosis). This response progressed through 90 days resulting in prominent neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly decreased in treated nerves. Early regenerative attempts were observed with strongly TH and growth-associated protein 43 positive and weak S100 disorganized nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100 staining. Evident growth-associated protein 43+ disorganized neuromatous tangles in the thickened perineurium of severed nerves were observed. At 90 days, some TH expression was observed together with prominent S100+ and growth-associated protein 43+ neuromatous tangles with disorganized architecture. The potential for regenerative activity is unlikely based on the disrupted architecture of these neuromatous tangles at the radiofrequency lesion sites. 

CONCLUSIONS:

This study is the first documentation that a progressive regenerative response occurs as early as 7 days after RDN, resulting in a poorly organized neuromatous regeneration. This finding is of paramount importance to further establish the potential functional significance of a regeneration after RDN.